Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. II. Terminal differentiation of postswitch sIgA-bearing Peyer's patch B cells.

Abstract

It is now well established that Peyer's patches (pp)l are lymphoid follicles that give rise to cells that are committed to IgA development and that ultimately localize in mucosal areas (1-5). However, the mechanisms governing such commitment are not completely understood. On the one hand, PP B cells and their clonal progeny could represent a class of B cells that secrete IgA, because they are exposed to a particular kind and pattern of specific (antigenic) and/or nonspecific (T cell and/or B cell) stimuli (6, 7); on the other hand, IgA B cells may develop in PP because PP contain Ig class-specific PP T cells that direct PP B cells along certain lines of differentiation (8, 9). Recently, we have provided additional evidence favoring the latter possibility, in that we have obtained T cell clones from PP which are capable of influencing PP B cell differentiation so that it follows a pathway that leads directly from IgM expression to IgA expression (10, 11). However, these IgA-specific T cells (switch T cells) cannot in themselves provide help for terminal differentiation of PP B cells since the effect of the switch T cells is to induce cells to become surface IgA-bearing B cells rather than plasma cells secreting IgA.Newer information regarding immunologic mechanisms governing B cell differentiation of all Ig classes are of relevance to IgA B cell differentiation. In this regard, there are extensive data which indicate that T cells or T cell-derived factors, and/or macrophages or macrophage-derived factors induced by specific and nonspecific stimuli can profoundly affect the proliferation and differentiation of T and/or B cells (12-26). These cells and the factors derived from these cells

Immunological Functions of the Gut–Role of the Mucosal Immune System

“…Considerable numbers of T cells of the helper phenotype coexist with B cells, and the processes of Ia-positive follicular dendritic cells are prominent in the germinal centers (20). This suggests that the germinal center is the site of immune responses to the antigens in the intestinal lumina, and of class switching from IgM to IgA of the patch B cells (22). Antigen-trapping by follicular dendritic cells and T cell regulation of B cell maturation have been well-documented (22,50).…”

“…The germinal center in Peyer's patch plays an important role in activation, proliferation, and heavy chain class switching during B cell responses (22). These primed or activated B lymphoblasts migrate to the mesenteric lymph node via the thoracic duct to the general circulation, and repopulate the intestinal mucosa (24).…”

“…Craig and Cebra (12) showed that Peyer's patches contain a concentration of precursors for subsequent differentiation into mature IgA plasma cells. Antigen challenge and exposure to bacterial lipopolysaccharides, for example, are known to force B cells in the Peyer's patches to eventually develop into IgA plasma cells (22).…”

Peyer’s Patches: Organized Lymphoid Structures for the Induction of Mucosal Immune Responses in the Intestine

“…Evidence that T cells regulate isotype differentiation at the level of naïve murine B cells comes from several sources. Kawanishi et al [143,144] demonstrated that sIgM + sIgA -B cells could be induced to switch sIgA + B cells in the presence of T cell clones derived from GALT. These sIgA + B cells could then be induced to secrete IgA in the presence of additional exoge-nous lymphokine [142].…”

Models to Follow Secretory IgA Response to Mucosal Infections

“…It is known that luminal antigen is taken up by specialized surface epithelial cells which overlie Peyer's patches, the appendix and isolated lymphoid follicles in the gut [3,4], This material stimulates underlying B lym phoblasts (which are enriched with precur sors for developing an IgA isotype). These cells leave the gut-associated lymphoid tis sues and migrate in turn to the mesenteric lymph nodes, the thoracic duct and eventu ally lodge in the spleen where they undergo some degree of maturation [5][6][7][8], During their maturation, they come under the in fluence of switch T cells which encourage the B lymphocytes to alter their isotype from pto a-heavy chain [9], Also, helper T cells which augment the IgA response are known to enhance the production of cells commit ted to IgA synthesis [10]. These B cells then travel to a variety of mucosal surfaces in cluding the gastrointestinal tract, bronchial mucosa, mammary glands and salivary glands.…”