Page 494 - Veterinary Immunology, 10th Edition

marrow. Once antigens activate the B cells, a second DNA
VetBooks.ir recombination event occurs. This second event results in a switch in

the class of BCR and thus antibodies produced by a B cell. This class
switch recombination does not affect the antigen-binding site.

Class Switch Recombination

During the course of a B cell response, the class of immunoglobulin
produced by a cell changes. This “class switch” can be explained by

the way in which heavy chain genes are assembled.
During an antibody response, the immunoglobulins are
synthesized in a standard sequence. Thus a responding B cell first
uses the IGHM gene to make IgM BCRs. The remaining genes
located 3′ to IGHM are ignored. In species that make IgD, the B cell

also transcribes the IGHD gene and then expresses both IgM and
IgD. As the immune response progresses, responding B cells switch
to using IGHG, IGHA, or IGHE genes and become committed to

synthesizing IgG, IgA, or IgE. The unwanted, unused IGH genes are
excised as a DNA circle and are lost from the cell, so that the
required IGH gene can be spliced directly to the IGHV gene.
For example, if IgM is to be synthesized, an IGHV gene is spliced
directly to the IGHM gene (Fig. 16.13). On the other hand, if IgA is

to be synthesized, the genes coding for Cµ to Cε inclusive are
deleted, and the IGHV gene is then spliced directly to the IGHA
gene. There are several ways by which these intervening genes can

be excised. The simplest is called looping out–deletion. In this case
the V region and C genes come together by looping out and then
excising the intervening DNA using an enzyme called a
recombinase. Two signals are needed to initiate class switching in a
B cell. First, the B cell must receive an activation signal generated

when CD40 on the B cell binds to CD154 on a helper T cell. Second,
the specific class switch is determined by signals from cytokines,
especially by IL-4, transforming growth factor-β (TGF-β), and

interferon-γ (IFN-γ). Signals from CD40 and the antigen activate
the recombinase in the B cell, while signals from the cytokine
receptors, by activating specific promoter regions, target the
recombinase to a specific heavy chain gene.

494