Page 662 - Veterinary Immunology, 10th Edition

lamina propria of the gut wall. They have fewer intraepithelial T
VetBooks.ir lymphocytes (IELs) within their intestinal epithelium. These IELs

have reduced expression of TLR and MHC class II, as well as
reduced cytotoxicity. Systemic immune defects are also apparent.
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Germ-free mice have fewer CD4 T cells in the spleen, and fewer
and smaller germinal centers as a result of reduced B cell numbers.
Their production of macrophages and neutrophils by bone marrow
stem cells is impaired. Their immunoglobulin levels are only about

2% of normal so that if exposed abruptly to the external
environment, they are vulnerable to bacterial diseases. The presence
of the microbiota is also necessary for the production of tertiary
lymphoid structures such as cryptopatches and isolated lymphoid

follicles.
Mammals have evolved two strategies to generate B cell
populations with a diverse antibody repertoire (Chapter 17). Thus
mice and humans rely mainly on random rearrangements of the VD

and J genes during B cell development within the bone marrow.
Other mammals such as cattle, sheep, pigs, and rabbits use an
alternative strategy. These species undertake an initial burst of B
cell proliferation with limited diversification in utero. These newly

produced cells then migrate to the gut-associated lymphoid tissues
where they expand both their numbers and their diversity. As
described in Chapter 12, in sheep the ileal Peyer's patch is the site of
B cell repertoire expansion, while the jejunal Peyer's patch is the

source of antigen-specific IgA responses.
The process of microbial-driven B cell diversification and IgA
production appears to depend upon the presence of a select
subgroup of bacteria within the microbiota. For example, a

combination of Bacteroides fragilis and Bacillus subtilis can induce B
cell development and VDJ diversification in germ-free rabbits.
Neither species alone has this effect, suggesting that two signals are
needed. Once B cell proliferation and diversification are triggered,

the microbiota continue to regulate any additional diversification. It
is believed that microbial molecules trigger these B cell responses
by binding to their TLRs and activating NF-κB pathways.
Alternatively, soluble bacterial superantigens might trigger a
polyclonal B cell response and drive the process by preferentially

stimulating the production of B cells expressing certain Vh regions.

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