T cells or their products are required for the differentiation of precursor B cells into antibody-secreting cells specific for a supposed T-independent self-antigen.
From our experiments and those of others in which cells were cultured at a density of 100,000 cells per well, it has been suggested that autoantibody production against mouse bromelain-treated erythrocytes (mouse brom-RBC) was independent of T cells, and further, was enhanced by the removal of T cells from responsive cell populations. Here it is shown in limiting dilution cultures that the autoimmune response is highly dependent on T cells or their products. B cells purified from the peritoneal cavities of untreated mice did not differentiate in vitro into autoantibody-secreting cells unless provided with signals from at least one of two types of accessory cells. These were plastic adherent cells and T cells, derived either from the peritoneal cavity or from established cell lines. Here it is shown that peritoneal T cells or T cells from the LBRM-33 cell line stimulated the differentiation of purified B cells in vitro in the absence of added mitogens. The accessory cell effect could be transferred in supernatants derived from T-cell cultures but not filler-cell cultures. Recombinant interleukin-2 (rIL-2) added to culture medium did not stimulate B cells directly, but could increase precursor frequencies when added to unfractionated peritoneal cell cultures, or B-cell cultures to which cells from a T-cell line had been added. From these results, it is concluded that the differentiation of precommitted peritoneal B cells in vitro into autoantibody secretors is at least partially dependent on T cells or lymphokines derived from them. Therefore, any proposed mechanisms for regulation of this autoimmune response should encompass the requirement for T cells or their products in the final differentiation stages to autoantibody secretion.
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D010529:Peritoneal Cavity / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D000955:Antigens, T-Independent; D001323:Autoantibodies; D001324:Autoantigens; D007376:Interleukin-2