CONTENTS

INTRODUCTION

B LYMPHOCYTES

ORIGIN OF B CELLS

DEVELOPMENT OF B CELLS

MATURATION OF B LYMPHOCYTES

STAGES OF LYMPHOCYTE MATURATION

TYPES OF B CELLS

DIFFERENTIATION OF B CELLS

PHASES OF ADAPTIVE IMMUNE RESPONSE

RECOGNITION OF ANTIGENS

ACTIVATION PHASE

T CELL INDEPENDANT RESPONSE

T CELL DEPENDANT RESPONSE

GENERATION OF PLASMA & MEMORY B CELLS

REGULATION OF HUMORAL IMMUNE RESPONSE

B CELL TOLERANCE

B CELLS IN PERIODONTITIS

B CELLS IN SYSTEMIC DISEASES

LABORATORY DIAGNOSIS

TREATMENT MODALITIES

CONCLUSION
INTRODUCTION
 Immunity-derived from Latin word ‘immunitas’ which means-protection from

disease. The cells and molecules responsible for immunity constitute the immune

system and the collective and coordinated response to the introduction of foreign

substance is called immune response. The most important physiologic function of

the immune system is to prevent or eradicate infections

Host defenses are grouped under innate immunity, which provides immediate

protection against microbial invasion, and adaptive immunity, which develops

more slowly and provides more specialized defense against infections

IMMUNITY

INNATE IMMUNITY ADAPTIVE IMMUNITY

Epithelium
Natural killer cells
Dendritic cells
HUMORAL CELL MEDIATED
Phagocytes
Mast cells (B cells) (T cells)

B LYMPHOCYTES

Lymphocytes are the only cells in the body capable of specifically recognising

and distinguishing different antigenic determinants and responsible for the two

defining characteristics of the adaptive immune response, specificity and memory.

They function in the humoral immunity component of the adaptive immune system
by secreting antibodies. Additionally B cells present antigen also classified as

professional antigen presenting cells. Murphy et al

ORIGIN OF B CELLS

In 1954,Bruce Glick in Ohio state university studied on the function of the

bursa of fabricus, a lymphoid organ in the cloacal region of the chicken. Bursa was
found to be the organ in which antibody producing cells were developed. He did
bursectomy and induced salmonella antigens. He found that bursectomised
chickens were not able to produce anti salmonella antibodies. Hence antibody
producing cells are called B cells. Mammals lack bursa and B cells are produced in
bone marrow.

DEVELOPMENT OF B CELLS
 B cells develop from hematopoietic stem cells (HSCs) that originate from

bone marrow. HSCs first differentiate into multipotent progenitor (MPP) cells,

then common lymphoid progenitor (CLP) cells. To complete development,

immature B cells migrate from the bone marrow to the lymphoid organs (LO) as

well as pass through two transitional stages: T1 and T2.

Throughout their migration to the spleen and after LO entry, they are

considered T1 B cells. Within the LO, T1 B cells transition to T2 B cells. T2 B

cells differentiate into either follicular (FO) B cells or marginal zone (MZ) B cells

depending on signals received through the BCR and other receptors. Chung,

Trends in Immunology.

MATURATION OF B LYMPHOCYTE

The maturation of B lymphocytes occurs mainly in the bone marrow. Progenitors

committed to the B cell lineage proliferate, giving rise to a large number of

precursors of B cells, called pro-B cells. Subsequent maturation involves antigen

receptor gene expression and selection.

Early Steps in B Cell Maturation.

The Ig heavy-chain locus rearranges first, and only cells that are able to make an

Ig μ heavy-chain protein are selected to survive and become pre-B cells. Some of

the μ protein is expressed on the cell surface in association with two other,

invariant proteins, called surrogate light chains because they resemble light chains

and associate with the μ heavy chain. The complex of μ chain and surrogate light

chains associates with the Igα and Igβ signaling molecules to form the pre-B cell

receptor (pre-BCR) complex.

Role of the Pre-BCR Complex in B Cell Maturation.

Signals from the pre-BCR complex promote the survival and proliferation

of B lineage cells that have made a productive rearrangement at the Ig H-chain

locus. This is the first checkpoint in B cell development, and it selects and expands

the pre-B cells that express a functional μ heavy chain (which is an essential

component of the pre-BCR and BCR). Pre-B cells that make out-of-frame

(nonproductive) rearrangements at the heavy-chain locus fail to make the μ protein,

cannot express a pre- BCR or receive pre-BCR signals, and die by programmed

cell death (apoptosis).

This receptor again delivers signals that promote survival, thus preserving

cells that express complete antigen receptors, the second checkpoint during

maturation.
Completion of B Cell Maturation.

The IgM-expressing B lymphocyte is the immature B cell. Its further

maturation may occur in the bone marrow or after it leaves the bone marrow and

enters the spleen. The final maturation step involves coexpression of IgD with IgM

Selection of mature repertoire

After immature lymphocytes express antigen receptors, the cells with

useful receptors are preserved & many harmful, self reactive cells are eliminated

by process of selection induced by antigen receptor engagement. The repertoire of

B lymphocytes is selected positively for expression of intact receptors and selected

negatively against strong recognition of self antigens.

STAGES OF LYMPHOCYTE MATURATION

Pro B cell:

 They do not produce Ig

 Express B lineage restricted surface molecules such as CD19 & CD10.

 RAG proteins are first expressed at this stage

 First recombination of Ig genes occurs in the heavy chain locus

Pre B cell:

 Synthesise a detectable Ig gene product(µ heavy chain)

 Some of the pre Bcells associate with surrogate light chains & form pre

Bcell receptors.

 Pre BCR associates with Iga & Igb protein molecules that function in

transducing signals from the receptor. Mulijo SA,Immunological

reviews2000

Immature B cell:

 IgM expressing B cell is called immature B cell.

 They do not proliferate & differentiate in response to antigens

Mature B cell:
  At this stage, the cells coexpress µ and ð heavy chains in association with

the k and λ light chain, thereby producing both membrane Ig M and Ig D.

 These mature,naïve B cells are responsive to antigens and unless the cells

encounter antigen,they die in a few days or weeks.

 Mature B cells are found in the circulation and peripheral lymphoid organs.

Nemazee et al

TYPES OF B CELLS

Plasmablast

They are short lived, generated early in an infection and their antibodies tend to
have a weaker affinity towards their target antigen

Plasma cells

They are long lived,generated later in an infection and their antibodies have a
higher affinity towards their target antigen

Memory B cell

They circulate through the body and initiate a stronger, more rapid antibody
response if they detect the antigen that had activated their parent B cell

B-1 cell

Arises from a developmental pathway different from FO B cells and MZ B

cells. A true homologue of mouse B-1 cells has not been discovered in humans

B2 cells

Follicular (FO) B Cell

 They are not circulating through the blood, is found mainly in the lymphoid

follicles of secondary lymphoid organs. Generates majority of high-affinity

antibodies during an infection.

Marginal zone (MZ) B cell

Found mainly in the marginal zone of the SLO and serves as a first line of

defense against blood-borne pathogens, as the marginal zone receives large

amounts of blood from the general circulation.

Regulatory B (Breg) cell

An immunosuppressive B cell type that stops the expansion of pathogenic,

pro-inflammatory lymphocytes through the secretion of IL-10, IL-35, and TGF-β.

It promotes the generation of regulatory T (Treg) cells. Roser et al

DIFFERENTIATION OF B CELLS

B cells participate in a two-step differentiation process that yields both short

lived plasmablasts for immediate protection and long-lived plasma cells and

memory B cells for persistent protection. David M. “The generation of antibody-

secreting plasma cells”. Nature Reviews Immunology.15 (3)

Extrafollicular response

It occurs outside of lymphoid follicles but still in the peripheral lymphoid

organs. Activated B cells proliferate, and differentiate into plasmablasts that
produce early, weak antibodies mostly of class IgM.
Follicular response

Activated B cells entering a lymphoid follicle and forming a germinal

center(GC) and generate both high affinity memory B cells and long-lived plasma
cells. Resultant plasma cells secrete large amounts of antibody and either stay
within the peripheral lymphoid organs or more preferentially,migrate to bone
marrow.

PHASES OF ADAPTIVE IMMUNE RESPONSE

RECOGNITION OF ANTIGENS

Humoral immune responses are initiated when antigen-specific B lymphocytes

in the spleen, lymph nodes, and mucosal lymphoid tissues recognize antigens.

Antigen-induced clustering of membrane Ig receptors triggers biochemical signals

that are transduced by receptor-associated signaling molecules

 Signal transduction by the B lymphocyte antigen receptor complex(BCR)

  Second signal provided by the complement

Signal transduction by the B lymphocyte antigen receptor complex(BCR)

BCR complex

The cytoplasmic domains of Igα and Igβ each contain a conserved

immunoreceptor tyrosine-based activation motif (ITAM), When two or more

antigen receptors of a B cell are clustered, the tyrosines in the ITAMs of Igα and

Igβ are phosphorylated by kinases associated with the BCR complex. These

phosphotyrosines recruit the Syk tyrosine kinase (equivalent to ZAP-70 in T cells),

which is activated and in turn phosphorylates tyrosine residues on adaptor proteins.

These phosphorylated proteins then recruit and activate a number of downstream

molecules, mainly enzymes that initiate signaling cascades that activate

transcription factors which switch on the expression of genes whose protein

products are involved in B cell proliferation and differentiation.

Signal transduction by complement

CR2-CD19-CD81

Bcell coreceptor

complex

B lymphocytes express a receptor for a protein of the complement system that

provides signals for the activation of these cells. When the complement system is
activated by a microbe, the microbe becomes coated with proteolytic fragments of
the most abundant complement protein, C3. One of these fragments is called C3d.
B lymphocytes express a receptor for C3d called complement receptor type 2
(CR2, or CD21). B cells that are specific for a microbe’s antigens recognize the
antigens by their BCRs and simultaneously recognize the bound C3d via the CR2
receptor. Engagement of CR2 greatly enhances antigen-dependent activation
responses of B cells.

ACTIVATION PHASE

There are two types of functional response of to antigen recognition upon

activation of b cells

 T cell independent response

 T cell dependant response

T CELL INDEPENDENT RESPONSE

Polysaccharides, Glycolipids, Nucleic acids, Natural antibodies elicit

antibody responses without the participation of helper T cells. These nonprotein

antigens cannot bind to MHC molecules, so they cannot be seen by T cells.

Antibody responses to T-independent antigens differ from responses to proteins.

They activate the complement system. The Antibody that is produced is Ig M to

some Ig G subtypes which are of Low affinity & show limited isotope switching
Structure of antibody

An antibody molecule is composed of four polypeptide chains—two

identical heavy (H) chains and two identical light (L) chains—with each chain

containing a variable region and a constant region. The four chains are assembled

to form a Y-shaped molecule. Each light chain is attached to one heavy chain, and

the two heavy chains are attached to each other, all by disulfide bonds. A light

chain is made up of one V and one C domain, and a heavy chain has one V and

three or four C domains. Each domain folds into a characteristic three-dimensional

shape, called the immunoglobulin (Ig) domain

The fragment of an antibody that contains a whole light chain (with its

single V and C domains) attached to the V and first C domains of a heavy chain
contains the portion of the antibody required for antigen recognition and is

therefore called Fab (fragment, antigen-binding). The remaining heavy-chain C

domains make up the Fc (fragment, crystalline) region; Between the Fab and Fc

regions of most antibody molecules is a flexible portion called the hinge region.

Antibodies are named according to their heavy chains such as μ, δ, γ, ε, and

α, which differ in their C regions

Heavy chain Light chain

 Ig A1,A2  Kappa-k

 Ig G1,G2a,G2b,G3,G4  Lambda-l

 Ig D  An Ab has either 2k/2l

 Ig E light chains but never of

each
 Ig M

Antibody is produced in

secreted form membrane form

(C region terminates with (C region is followed by 26 AA

charged & hydrophilic AA) with hydrophobic residues)

Antibody

isotopes Effector functions

Neutralization of microbes and toxinsOpsonization of antigens

for phagocytosis by macrophages and neutrophilsActivation of
Ig G
the classical pathway of complementAntibody-dependent
cellular cytotoxicity mediatedby NK cellsNeonatal immunity:
transfer of maternal antibodyacross placenta and gutFeedback
inhibition of B cell activation
Mucosal immunity: secretion of IgA into lumens
Ig A ofgastrointestinal and respiratory tracts, neutralization of
microbes and tox
Ig M Activation of the classical pathway of complemen
IgE Eosinophil- and mast cell-mediated defense against helminths

Ig D Antigen receptor for naïve B cells

COMPLEMENT SYSTEM

The name of the complement system is derived from experiments performed by

Jules Bordet shortly after the discovery of antibodies. When antibacterial

antibodies are induced at 37 C to a bacteria it caused lysis. When these Ab are

heated at 56 C and then induced to bacteria, there was no lysis. It is known that

Antibodies are heat stable. Therefore Bordet concluded that serum must contain

another heat labile component that complements the lytic function of antibodies

and hence the name complement.

Pathways of complement activation

 Classical pathway

(activated by Ag-Ab complex)

 Alternative pathway

(activated on the microbial cell surface in the absence of antibody)

 Lectin pathway

(activated by plasma lectin) Carroll MC 1998

CLASSICAL PATHWAY

The classical pathway of complement activation is triggered when IgM or

certain subclasses of IgG (IgG1, IgG2, and IgG3 in humans) bind to antigens (e.g.,

on a microbial cell surface). As a result of this binding, adjacent Fc regions of the

antibodies become accessible to and bind the C1 complement protein (which is

made up of a binding component called C1q and two proteases called C1r and
C1s). The attached C1 becomes enzymatically active, resulting in the binding and

sequential cleavage of two proteins, C4 and C2. One of the C4 fragments that is

generated, C4b, becomes covalently attached to the antibody or to the microbial

surface where the antibody is bound, and then binds C2, which is cleaved by active

C1 to yield the C4b2a complex. This complex is the classical pathway C3

convertase, which functions to break down C3, and the C3b that is generated again

becomes attached to the microbe. Some of the C3b binds to the C4b2a complex,

and the resultant C4b2a3b complex functions as a C5 convertase, which cleaves

the C5 complement protein.

ALTERNATIVE PATHWAY

The alternative pathway of complement activation is triggered when a

breakdown product of C3 hydrolysis, called C3b, is deposited on the surface of a

microbe. Here, the C3b forms stable covalent bonds with microbial proteins or

polysaccharides and is thus protected from further degradation. The microbe-

bound C3b binds another protein called Factor B, which is then broken down by a

plasma protease called Factor D to generate the Bb fragment. This fragment

remains attached to C3b, and the C3bBb complex functions as an enzyme, called

the alternative pathway C3 convertase, to break down more C3. The C3 convertase

is stabilized by properdin, a positive regulator of the complement system. As a

result of this enzymatic activity, many more C3b and C3bBb molecules are

produced and become attached to the microbe. Some of the C3bBb molecules bind
an additional C3b molecule, and the resulting C3bBb3b complexes function as C5

convertases, to break down the complement protein C5 and initiate the late steps of

complement activation.

LECTIN PATHWAY

It is triggered in the absence of antibody by the binding of microbial

polysaccharides to circulating lectins such as mannose binding lectin which is

structurally similar to C1q. Apart from being activated in the absence of antibody,

it is similar to classical pathway.

T CELL DEPENDANT RESPONSE

B cell activation by antigen (and other signals) initiates the proliferation and

differentiation of the cells and prepares them to interact with helper T lymphocytes

if the antigen is a protein. For a protein antigen to stimulate an antibody response,

B lymphocytes and helper T lymphocytes specific for that antigen must come

together in lymphoid organs and interact in a way that stimulates B cell

proliferation and differentiation.

Activation and Migration of Helper T Cells

Helper T cells that have been activated by dendritic cells migrate toward the

B cell zone and interact with antigen-stimulated B lymphocytes in parafollicular

areas of the peripheral lymphoid organs. The antigens that stimulate CD4+ helper

T cells are proteins derived from microbes that are internalized, processed in late

endosomes and lysosomes, and displayed bound to class II major

histocompatibility complex (MHC) molecules of APCs in the T cell– rich zones of

peripheral lymphoid tissues. The CD4+ T cells differentiate into effector cells

capable of producing various cytokines and some of these T lymphocytes migrate

toward the edges of lymphoid follicles. B lymphocytes are activated by antigen in

the follicles and begin to move out of the follicles toward the T cells.

COSTIMULATION

The directed migration of activated B and T cells toward one another

depends on changes in the expression of certain chemokine receptors on the

activated lymphocytes. Activated T cells reduce expression of the chemokine

receptor CCR7, which recognizes chemokines produced in T cell zones, and

increase expression of the chemokine receptor CXCR5, which promotes migration

into B cell follicles. Activated B cells undergo precisely the opposite changes,

decreasing CXCR5 and increasing CCR7 expression. As a result, antigen-

stimulated B and T cells migrate toward one another and meet at the edges of

lymphoid follicles or in interfollicular areas.

Role of costimulation in T cell activation

The full activation of T cells depends on the recognition of costimulators on

APCs in addition to antigen. The best-defined costimulators for T cells are two

related proteins called B7-1 (CD80) and B7-2 (CD86), both of which are expressed

on APCs and whose expression is increased when the APCs encounter microbes.

These B7 proteins are recognized by a receptor called CD28, which is expressed

on most T cells. Different members of the B7 and CD28 families serve to stimulate

or inhibit immune responses. The binding of CD28 on T cells to B7 on the APCs

generates signals in the T cells that work together with signals generated by TCR

recognition of antigen presented by MHC proteins on the same APCs.

Presentation of Antigens by B Lymphocytes to Helper T Cells

The B lymphocytes that bind protein antigens by their membrane Ig antigen

receptors endocytose these antigens, process them in endosomal vesicles, and

display class II MHC–associated peptides for recognition by CD4+ helper T cells

 A hapten is a small chemical that is recognized by B cells but stimulates

strong antibody responses only if it is attached to a carrier protein. In this situation

the B cell binds the hapten portion, ingests the conjugate, and displays peptides

derived from the carrier to helper T cells. This concept has been exploited to

develop effective vaccines against microbial polysaccharides. Some bacteria have

polysaccharide-rich capsules, and the polysaccharides themselves stimulate T-

independent antibody responses, which are weak in infants and young children. If

the polysaccharide is coupled to a carrier protein, however, effective T-dependent

responses are induced against the polysaccharide because helper T cells specific

for the carrier are engaged in the response. Such conjugate vaccines have been

very useful for inducing protective immunity against bacteria such as Haemophilus

influenzae, especially in infants.

Mechanism of helper T cell mediated B cell activation

Activated helper T lymphocytes that recognize antigen presented by B cells

use CD40 ligand (CD40L) and secreted cytokines to activate the antigen-specific B

cells. CD40L expressed on activated helper T cells binds to CD40 on B

lymphocytes. Engagement of CD40 delivers signals to the B cells that stimulate

proliferation and the synthesis and secretion of antibodies. At the same time,

cytokines produced by the helper T cells bind to cytokine receptors on B

lymphocytes and stimulate more B cell proliferation and Ig production.

Extrafollicular and Germinal Center Reactions

Many of the events in fully developed antibody responses occur in germinal

centers that are formed in lymphoid follicles and require the participation of a

specialized type of helper T cell. A few of the activated B cells from the extra-

follicular focus migrate back into the lymphoid follicle and begin to divide rapidly

in response to signals from Tfh cells. It is estimated that these B cells have a

doubling time of approximately 6 hours, so one cell may produce several thousand
progeny within a week. The region of the follicle containing these proliferating B

cells is the germinal center

B cells that have been activated by T helper cells at the edge of a primary

follicle migrate into the follicle and proliferate, forming the dark zone of the

germinal center. Germinal center B cells undergo extensive isotype switching and

somatic mutation of Ig genes, and migrate into the light zone, where B cells with

the highest affinity Ig receptors are selected to survive, and they differentiate into

plasma cells or memory cells, which leave the germinal center.

EFFECTOR PHASE OF T CELL DEPENDANT IMMUNE

RESPONSE

Antigen-stimulated B

lymphocytes may differentiate

into IgM antibody-secreting cells, or, under the influence of CD40 ligand (CD40L)

and cytokines, some of the B cells may differentiate into cells that produce

different Ig heavy-chain isotypes. The principal effector functions of some of these

isotypes are listed; all isotypes may function to neutralize microbes and toxins.

BAFF is a B cell–activating cytokine that may be involved in switching to IgA,

especially in T-independent responses. Switching to IgG subclasses is stimulated

by the cytokine interferon (IFN)-γ in mice, but in humans it is thought to be

stimulated by other cytokines. IL-4, Interleukin-4; TGF-β, transforming growth

factor β.

Affinity maturation

Affinity maturation is the process by which the affinity of antibodies

produced in response to a protein antigen increases with prolonged or repeated

exposure to that antigen. Because of affinity maturation, the ability of antibodies to

bind to a microbe or microbial antigen increases if the infection is persistent or

recurrent. Affinity maturation occurs in the germinal centers of lymphoid follicles

and is the result of somatic hypermutation of Ig genes in dividing B cells, followed

by the selection of high-affinity B cells by antigen

Some activated B cells migrate into follicles to form germinal centers, where

they undergo rapid proliferation and accumulate mutations in their immuno-

globulin (Ig) V genes. These B cells produce antibodies with different affinities for

the antigen. Follicular dendritic cells (FDCs) display the antigen, and B cells that

recognize the antigen are selected to survive. FDCs display antigens by utilizing Fc

receptors to bind immune complexes. B cells also bind the antigen, process it, and

present it to follicular helper T (Tfh) cells in the germinal centers, and signals from

the Tfh cells promote survival of the B cells. As more antibody is produced, the

amount of available antigen decreases, so only the B cells that express receptors

with higher affinities can bind the antigen and are selected to survive.

GENERATION OF PLASMA CELLS AND MEMORY B CELLS

Activated B cells in germinal centers may differentiate into long-lived

plasma cells or memory cells. The antibody-secreting cells enter the circulation

and are called plasmablasts. From the blood they tend to migrate to the bone

marrow or mucosal tissues, where they may survive for years as plasma cells and

continue to produce high-affinity antibodies, even after the antigen is eliminated. It

is estimated that more than half of the antibodies in the blood of a normal adult are

produced by these long-lived plasma cells; often are the progeny of isotype-

switched high-affinity B cells, do not differentiate into active antibody secretors

but instead become memory cells. Memory B cells do not secrete antibodies, but

they circulate in the blood and reside in mucosal and other tissues. They survive

for months or years in the absence of additional antigen exposure, undergo slow

cycling, and are ready to respond rapidly if the antigen is reintroduced. Therefore,

memory from a T-dependent antibody response can last for a lifetime.

REGULATION OF HUMORAL IMMUNE RESPONSE

ANTIBODY FEEDBACK

B cells specific for the antigen may bind the antigen part of the immune

complex by their Ig receptors. At the same time, the Fc tail of the attached IgG

antibody may be recognized by a special type of Fc receptor expressed on B cells

(as well as on many myeloid cells) called FcγRIIB contains an ITIM that binds

enzymes that inhibit antigen receptor–mediated B cell activation. ITAM, Im-

munoreceptor tyrosine-based activation motif; ITIM, immunoreceptor tyrosine-

based inhibition motif. This Fc receptor delivers inhibitory signals that shut off

antigen receptor–induced signals, thereby terminating B cell responses. This

process, in which antibody bound to antigen inhibits further antibody production, is

called antibody feedback.

B CELL TOLERANCE

Tolerance in B lymphocytes is necessary for maintaining

unresponsiveness to thymus independent self antigens, polysaccharides and lipids.

 Central tolerance

 Peripheral tolerance
Central tolerance

Immature B lymphocytes that recognise self antigens in the bone

marrow with high affinity either are deleted or change their specificity. The

principal mechanism of immature B cells that encounter multivalent self antigens

is apoptotic. It may also respond by reactivating their RAG1,RAG2 genes and

express a new Ig light chain, acquiring a new specificty, called receptor editing

Peripheral tolerance

Mature lymphocytes that recognise self antigens in peripheral tissues

in the absence of specific helper T cells may be rendered functionally unresponsive

or are excluded from lymphoid follicles. Anergic B cells are incapable of

activating tyrosine kinases such as Syk. They also lose their capacity to migrate

into lymhoid follicles .

B CELLS IN PERIODONTITIS

B cell progression from gingivitis to periodontits

In 1976 Page & Schroeder classified the progression of gingival to

periodontal inflammation as follows:

1. Intial lesion: predominant with PMN’s.

2. Early lesion: T cells ↑, B cells, lymphocytes & PMN’s more than plasma cells
3. Established lesion: B cells↑, T cells↓, plasma cells predominant. 2 types of
established lesion appear to exist:

 stable & not progress for months/yrs (Lindhe et al 1975, Page et al 1975)

 active- progressive advanced lesion

Seymour et al (1979) hypothesized that a change from T cell to B cell

dominance, converted it from stability to activity involving aggressive destruction.

Page (1986) Gillette et al (1986) disagreed. Showed that B cell infiltrate mainly

was associated with non progressive lesion in childhood gingivitis.

Liljenberg et al ( 1994) compared plasma cell density & found the density of

plasma cell(51.3%) was very much increased in active sites as compared to

inactive sites.

4. Advanced lesion: It is generally accepted that plasma cells are predominant type

in advanced lesions ( Garant & Mulvihill,1972)

Ab’s response to P.gingivalis & A.actinomycetemcomitans are increased in pts

with periodontal disease than without . ( Kinane et al 1993, Mooney et al 1994)

Naito et al (1987) demonstrated that the serum titer to P.g was decreased in

periodontitis pts following successful therapy.

Mooney et al (1995) conducted a study on specific Ab avidity to P.g & A.a in

periodontitis patients before & after periodontal therapy. Results :In patients who
had originally high levels of IgG & IgA to P.g had demonstrated better treatment

outcomes.

Seymour & Greenspan(1979) reported that majority of the lymphocytes had the

phenotype of B cells and were positive for IgM & IgG.

Lindhe et al(1980) – Periodontitis lesion: 31%plasma cells, 5-

10%lymphocytes, 5%fibroblast, 1.3%macrophages, 1.3%neutrophil. In the

gingivitis lesion the ratio lymphocytes-plasma cells was 1:1,in periodontitis-1:3.

Okada et al(1983) Only few PMNs were observed. Plasma cells predominated

in the central portion of the lamina propria,with the proportion positive for

IgG,IgA & IgM accounting for 65.2%,11.2% & 1.3% of the total infiltrating cells.

Gillett et al(1986) : In juvenile periodontitis biopsies,>50% of the cells were

plasma cells. Lesions in chronic adult periodontitis were dominated by Bcells &

plasma cells.

Morinushi et al (2000 ) showed that serum anti P. gingivalis but not anti A.a

antibodies were inversely correlated with gingival inflammation, suggesting an

inhibition of P.gingivalis antibodies.

Berglundh T, Donati M (2005) found that in periodontitis lesion, plasma cells

most common-50% of all cells. B cells-18%. Proportion of B cells larger than T

cells. The relative dominance of B cells & plasma cells may be because of

imbalance between Th1 & Th2.

B CELLS IN SYSTEMIC DISEASES

B cell deficiency leads to different types of diseases like

X linked agammaglobulinemia

Ig A deficiency

IgG subclass deficiency

Immunodeficiency with increased IgM

Common variable variable immunodeficiency

Transient hypoglammaglobulinemia

LABORATORY DIAGNOSIS

Laboratory methods using antibodies

1.quantitation of antigens by immunoassays

-Enzyme liked immunosorbent assays(ELISA)

-Radioimmunoassay(RIA)

2. Purification and identification of proteins

-Immunoprecipitation and affinity chromatography.

-Western blotting.

3.Labelling and detection of antigens in cells and tissues

 -Flow cytometry

-Florescence activated cell sorting

-Immunofluorescence

-Immunohistochemistry

4.Measurement of antigen antibody interactions

-Equilibrium dialysis.

Analysis of gene structure and expression

1. Southern blot hybridization

2.Northern blot hybridization

3.Rnase protection assays

4.Polymerase chain reaction

Transgenic mice and Targeted gene knockouts

TREATMENT MODALITIES

The two main aims of current treatment modalities are

-to minimize and control infections

-to replace the defective or absent components of the immune system by

adoptive transfer or transplantation. MC Michael AJ.,2001

 Treatment of congenital diseases involves transfusion of antibodies.

  Bone marrow transplantations.

 Autologous stem cell transplantation helps in restoration of immunologic

self tolerance.

 Enzyme replacement therapy.

 Gene therapy may offer improved treatments in the future. Meischl C.,1998

CONCLUSION

It is evident that B cells and plasma cells dominate among cells in

periodontitis. A balance between the protective and destructive nature of B cells

determine the periodontal disease susceptibility. This balance is dependent on

genetic, systemic, microbial and other local factors.

Proper understanding of these inter relationship help us in deriving

newer therapeutic strategies, which may benefit high risk individuals.

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