B Cells

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Overview of B cell Development

Signals from bone


marrow stromal cells.
e.g, IL-7, CXCL12. c- Immuno-competent
kit mature B cells expressing
mIgM & mIgD
- Help in induction of
primary Transcription
factors required for B
cell development

Activation of B cells: T
cell dependent and T
cell independent
Germinal Centers:
In Spleen and
Lymph nodes

Kuby Fig. 11.1


Stages of B cell development
TF: PAX5 1st Check point
Blocking of non B cell lineage proteins *Pre BCR signaling

Pre-Pro B Cell Early pro-B cell Late pro-B cell Large pre-B cell
TF: EBF1 &E2A
- Expression of B cell proteins 2 Check point
nd

Expression of mIgM Spleen

T1 B cells T2 B cells
-ve selection +ve selection by
Small/Late pre-B cell Immature B cell BAFF signaling
Negative selection in BM

Mature B cell
Ligation of the pre-B cell receptor
* Pre-BCR: Arranged μ heavy chain +Surrogate light chain

Large Unconfirmed ligand of


Pre-B pre-B cell receptor

1. Suppresses further H chain rearrangement


2. Proliferation
Stromal cell 3. Rearrangement of light chain

• Pre-B cell receptor ligation is essential for B cell development


• B cells have several opportunities to rearrange their antigen receptors
• Negative selection is less Stringent in B cells compared to T cells
• Receptor Editing: Immature B cells with mIgM are susceptible to tolerance induction. If
they encounter any self antigen, they re express RAG-1 and RAG-2 genes and edit their
light chain

• B cells are named as B1 and B2 cells. B1 cells protect gut and lungs and their antibodies
cross react with protein and carbohydrate antigens. They are self renewing. Bridge
between innate and adaptive immune system
Plasma cells

Surface Surface High rate Growth Somatic Isotype


Ig MHC II Ig secretion hypermut’n switch

B High Yes No Yes Yes Yes


Mature B cell

B
Low No Yes No No No
Plasma cell
B Cell Activation by T independent and T
dependent antigen

Mitogen, Polyclonal B cell activators • Direct contact with T helper cells


e.g, LPS • Class switch Recombination, Somatic
Cross link mIgM and mIgD. Hypermutaion and memory formation
Also involve other receptors such as
PRRs
Kuby Immunology
Movement of antigen specific T and B cells within the
lymph node after antigen encounter

Kuby Fig. 12-9 Pg. 394

Following antigen encounter, B cells travel to the T cell rich area and present antigen to
the T cell specific of the same antigen
Main steps during B-cell activation by a thymus-dependent
antigen:

• Soluble protein antigens which bind to membrane bound


immunoglobulin on the surface of B Cell are internalized,
processed and are displayed as peptide-MHC-II complexes.
• TH cell recognizes class II MHC-antigen complex on B-cell
surface via TCR. It also interacts with costimulatory
molecule B7 via CD28. These interactions activates TH cell.
Activated TH cells produces various cytokines.
• TH cell begins to express CD40L and interacts with CD40 of
the B Cell. The interaction between CD40 and CD40L
provides second signal to activate B cell.
• B cells begins to express receptors for various cytokines
and binds to cytokines released from TH cells. Which
activates B cell and differentiates them to plasma cells.
• The activated B-cell clonally proliferates to produce a
population of plasma cells and memory cells, which all
recognize the same antigen
• This CD40/CD40L interaction is essential for B-cell survival,
the formation of germinal centers, the generation of
memory-cell populations and somatic hypermutation (for
affinity maturation).
SHM occurs only in the variable region of the heavy and the light chains
Kuby Pg. 403
Kuby Pg 405

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