Page 452 - Veterinary Immunology, 10th Edition

In most newborn mammals, each B cell initially expresses both
VetBooks.ir IgM and IgD BCRs on its surface, with about 10 times as many IgD

molecules as IgM. These unstimulated B cells may secrete small
amounts of monomeric IgM.

When appropriately stimulated and co-stimulated, B cells
undergo repeated division. The B cell division that results from this
is asymmetric so that one daughter cell gets lots of antigen while
the other daughter cell gets very little or none. The cell that gets lots

of antigen then differentiates into a plasma cell. The cell that gets
none continues the cycle of dividing and mutating and eventually
becomes a memory cell. The cells destined to become plasma cells
develop a rough endoplasmic reticulum, increase their rate of

synthesis, and secrete large quantities of immunoglobulins. Within
a few days, these responding cells switch from making IgM to
making another immunoglobulin class. This switch occurs within
the germinal center and leads to production of IgG, IgA, or IgE. The

class switch results from deletion of unwanted heavy chain genes
and the joining of variable-region genes to the next available heavy
chain genes (Chapter 16). The specificity of the antibody produced
remains unchanged.

Class switching is controlled by IL-4, IFN-γ, and TGF-β. Thus IL-
4 from Th2 cells directs mouse B cells to produce IgG1 and IgE,
whereas it directs human B cells to produce IgG4 and IgE (see Table
15.1). IL-4 alone is insufficient for class switching, and additional

signals are required from CD40 and CD154. IFN-γ from Th1 cells
stimulates a switch to IgG2a and IgG3 in mouse B cells and
effectively suppresses the effects of IL-4. IFN-γ acts by promoting
the production of the B cell-stimulating cytokines BAFF and APRIL

(Box 15.2). TGF-β promotes the switch to IgA production on body
surfaces. As described previously, signals from IL-5, IL-6, IL-13, and
IL-21 also contribute to class switching.

Box 15.2

BAFF/APRIL System

B cell activating factor (BAFF; CD257) and “a proliferation-
inducing ligand” (APRIL; CD256) are two related cytokines. BAFF

is produced by monocytes, dendritic cells, T cells, and neutrophils.

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