Human germinal center CD4+CD57+ T cells act differently on B cells than do classical T-helper cells.
We have isolated two subtypes of helper T cells from human tonsils: CD4+CD57+ cells, mostly located in the germinal center (GC), and CD4+CD57- cells, distributed through the interfollicular areas but also present in the GC. In a functional study, we have compared the capacities of these T-cell subtypes to stimulate B cells in cocultures. In order to block T-cell proliferation while maintaining their activation level, we pretreated isolated T cells with mitomycin C prior to culture in the presence of B cells and added polyclonal activators such as PHA and Con A, combined or not with IL-2. Contrary to CD4+ CD57- cells, CD4+CD57+ cells did not markedly enhance B-cell proliferation. Even when sIgD.B cells typical of germinal center cells were tested, the CD4+CD57+ cells had no significant effect. This is in accordance with the location of these cells: They mainly occupy the light zones of the GC where few B cells divide. Even when added to preactivated, actively proliferating cells, CD4+CD57 cells failed to modulate B-cell multiplication. On the supernatants of B-cell-T-cell cocultures, we examined by the ELISA technique the effect of T cells on Ig synthesis. Contrary to CD57+ T cells, whose effect was strong, CD57- T cells weakly stimulated Ig synthesis. More IgM than IgG was generally found. Because CD57 antigen is a typical marker of natural killer cells, we tested the cytolytic activity of tonsillar CD4+CD57+ cells on K562 target cells. Unlike NK cells, neither CD4+CD57+ nor CD4+CD57- cells exhibit any cytotoxicity. Thus, germinal center CD4+CD57+ cells are not cytolytic and do not strongly stimulate either B-cell proliferation or Ig secretion. CD4+CD57- cells, however, enhance B-cell proliferation and differentiation, thus acting like the classical helper cells of the T-dependent areas.
Bouzahzah
F
F
Institute of Human Histology, University of Liège, Belgium.
Bosseloir
A
A
Heinen
E
E
Simar
L J
LJ
D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018959:CD57 Antigens / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D014066:Palatine Tonsil / Q000166:cytology* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D018959:CD57 Antigens; D007136:Immunoglobulins