The mucosal B-cell system

Abstract

The mucosal B-cell system forms the adaptive basis for humoral immune defense of the extensive mucosae. Such antibody protection depends on a complex cooperation between local B cells and secretory epithelia. Mucosa-associated lymphoid tissue (MALT) gives rise to activated B cells with striking J-chain expression that are seeded to local and distant secretory effector sites. Such homing is the biological prerequisite for local plasma cell (PC) production of polymeric immunoglobulin A (pIgA, mainly dimers) and pentameric IgM with high affinity to the epithelial pIg receptor that readily can export these antibodies to the mucosal surfaces. The J chain is also produced by IgG- and IgD-producing PCs occurring at secretory tissue sites; these PC isotypes may be considered as 'spin-offs' from early effector clones that through class switch are on their way to pIgA production. Abundant evidence supports the notion that intestinal PCs are largely derived from B cells initially activated in gut-associated lymphoid tissue (GALT). Nevertheless, insufficient knowledge exists concerning the relative importance of M cells, major histocompatibility complex class II-expressing epithelial cells, and professional antigen-presenting cells for the uptake, processing, and presentation of luminal antigens in GALT to accomplish the extensive and sustained priming and expansion of mucosal B cells. Also, it is unclear how the germinal center reaction in GALT so strikingly can promote class switch to IgA and expression of J chain, but the commensal microbiota appears to contribute to both the diversification and memory of MALT responses. Although B-cell migration from GALT to the intestinal lamina propria is guided by rather well-defined adhesion molecules and chemokines/chemokine receptors, the cues directing preferential homing to different segments of the gut require better definition. This is even more so for the molecules involved in homing of mucosal B cells to secretory effector sites beyond the gut. In this respect, the role of Waldeyer's ring (including the palatine tonsils and adenoids) as a regional MALT in humans needs further characterization, although the balance of evidence suggests that it functions as nasopharynx-associated lymphoid tissue (NALT) identified in rodents. Altogether, data suggest a remarkable compartmentalization of the mucosal immune system that must be taken into account in the development of effective local vaccines to protect specifically the airways, eyes, oral cavity, small and large intestines, and female genital tract.