Evolution of B cell immunity

Abstract

Two types of adaptive immune strategies are known to have evolved in vertebrates: the VLR-based system, which is present in jawless organisms and is mediated by VLRA and VLRB lymphocytes, and the BCR/TCR-based system, which is present in jawed species and is provided by B and T cell receptors expressed on B and T cells, respectively. Here we summarize features of B cells and their predecessors in the different animal phyla, focusing the review on B cells from jawed vertebrates. We point out the critical role of nonclassical species and comparative immunology studies in the understanding of B cell immunity. Because nonclassical models include species relevant to veterinary medicine, basic science research performed in these animals contributes to the knowledge required for the development of more efficacious vaccines against emerging pathogens.

Figure 1

Antibody diversification mechanisms. In addition to the combinatorial diversity of variable (diversity) joining [V(D)J] segments and heavy/light chains, antibodies are diversified by different mechanisms, including gene conversion, somatic hypermutation, and class switch recombination. The main enzymes implicated in each process are shown in orange. Animal names represent species in which a mechanism has been experimentally demonstrated. Abbreviations: AID, activation-induced cytidine deaminase; GALT, gut-associated lymphoid tissue.

Figure 2

Immunoglobulin (Ig) repertoire diversification in rodents/primates and gut-associated lymphoid tissue (GALT) mammals. In primates and rodents, V_H genes from many V_H families rearrange to one diversity (D) and one joining (J) segment, which thus leads to the generation of enormous diversity through combinatorial joining and the rearrangement process itself (junctional diversity). In the GALT species, a single or very few variable (V) genes rearrange with D and J segments, generating a poor repertoire that is further modified and amplified in the GALT (e.g., the ileum Peyer's patches in sheep and the appendix in rabbit) in a nonantigen-dependent process. After antigen encounter and as a secondary response, the mammalian repertoire is diversified by somatic hypermutation (SHM) in rodents and primates and SHM and gene conversion in GALT mammals. Abbreviation: C, constant region.

Figure 3

Hypothetical roles of phagocytic B-1 B cells. In peritoneal cavity (PerC), B-1 B cells phagocytose apoptotic bodies (purple arrows) generated from apoptotic cells, which may lead to the secretion of IL-10 by these cells. Subsequent antigen presentation of epitopes from apoptotic bodies will likely induce T cell tolerance. In a different scenario, and as a result of injury or inflammatory damage, commensal bacteria may leak from the gut lumen into the PerC, where phagocytic B-1 B cells engulf them (green arrows). Alternatively, these cells could phagocytose pathogenic bacteria that have intruded into the PerC (red arrows). As result, phagocytic B-1 B cells may secrete polyreactive immunoglobulin M (IgM), which can recognize either leaked commensals or pathogenic microbes found in the PerC. It is also possible that after clonal expansion, they secrete specific antibodies against pathogenic bacteria. In addition, some of the secreted IgM may recognize self-antigens and thus play a role in autoimmunity. After ingesting commensals or pathogens, phagocytic B-1 B cells may migrate into the gut lamina propria (pink arrow) or the spleen or peripheral lymph nodes (blue arrows). In those sites, the phagocytic B cells may produce polyreactive IgM or IgA [after class switch recombination (CSR)]. The produced IgA and IgM will be transported into the gut lumen (dashed arrow) to coat commensals, thus playing a role in immune exclusion. In addition, phagocytosis by B-1 B cells may lead to their expression of proinflammatory cytokines in PerC, spleen, and lymph nodes, whereas their expression of anti-inflammatory cytokines is less likely (indicated in gray with question mark). Conversely, production of anti-inflammatory cytokines by phagocytic B-1 B cells that have migrated into the gut lamina propria likely is more probable than production of proinflammatory cytokines.