Regulation of IgA secretion by T cell clones derived from the human gastrointestinal tract.
The role of T cells in Ig isotype regulation is still unclear. To address this question, we generated mitogen-stimulated T cell clones from normal human lymphoid follicles of the gut-associated lymphoid tissue (appendix). Both the T cell clones and clonal supernatants provided preferential help for IgA secretion by PWM-stimulated B cells. Many of these CD3+, CD4+, 4B4+, DR+ helper clones co-expressed Fc-gamma and Fc-alpha R, but there was poor correlation between the expression of Fc-alpha R and IgA help (p = 0.31). Most of the T cell clones helped both IgM+A- and IgM-A+ B cell populations to secrete IgA, suggesting that they mediate switch of isotype-uncommitted B cells as well as post-switch expansion of IgA-committed B cells; however, some of the T cell clones helped IgM+A- B cell populations much more than IgM-A+ B cell populations, suggesting that, in this case, the regulatory effect is predominantly at the level of B cell switch. In all, these results show that the mucosal immune system contains individual T cells which are capable of positively regulating IgA-specific isotype differentiation at two levels of B cell development, thus allowing for efficient generation of IgA-secreting B cells.
Benson
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EB
Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Strober
W
W
D000328:Adult; D001065:Appendix; D001402:B-Lymphocytes / Q000145:classification / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000378:metabolism*; D007075:Immunoglobulin M / Q000032:analysis; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008211:Lymphocyte Cooperation; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D011961:Receptors, Fc / Q000032:analysis; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D008222:Lymphokines; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc