Page 617 - Veterinary Immunology, 10th Edition

VetBooks.ir B Cell Tolerance

Unlike the TCR repertoire, B cell antibody diversity is generated in
two phases. The first phase involves VDJ rearrangement or gene

conversion in the primary lymphoid organs; the second phase
involves random somatic mutation in secondary lymphoid organs.
B cells therefore have several opportunities to generate receptors
that can bind self-antigens. It has been estimated that 55% to 75% of
early immature B cells have self-reactive receptors, so suppression

of these B cells must begin at an early stage in an animal's
development.
Immature B cells in the bone marrow can be made tolerant once

they have rearranged their V-region genes and are committed to
express complete immunoglobulin M (IgM) molecules. When these
immature cells encounter and bind antigen, the BCR transmits a
signal that arrests cell development, blocks synapse formation, and
triggers apoptosis. An immature B cell population can be rendered

tolerant by one millionth of the dose of an antigen required to make
mature B cells tolerant. Immature B cells may also undergo receptor
editing as described previously. If receptor editing fails to generate

a non–self-reactive B cell, it will die.

Peripheral B Cell Tolerance

Peripheral B cell tolerance is induced by multiple mechanisms
including apoptosis, clonal anergy, clonal exhaustion, and blockage

of BCRs.
Because BCRs undergo random somatic mutation within
germinal centers, self-reactive B cells will develop in secondary
lymphoid organs. These cells will not, however, make

autoantibodies if APCs and helper T cells are absent or if Treg cells
are active (Fig. 20.7). This is not, however, a foolproof method of
preventing self-reactivity. In the absence of T cell help, B cells may
be activated by PAMPs such as LPS, flagellins, or unmethylated

CpG DNA acting through TLRs. B cells may also be activated by
either cross-reacting epitopes or by foreign carrier molecules
stimulating non-tolerant helper T cells (see Fig. 36.2).

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