Genetic control of immune response to myoglobin. Ir gene function in genetic restriction between T and B lymphocytes.

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Abstract
The genetic restrictions on the interaction between T cells, B cells and antigen-presenting cells (APC) involved in the H-2-linked Ir gene control of the in vitro secondary antibody response to sperm whale myoglobin (Mb) in mice were studied. The B cells in this study were specific for Mb itself, rather than for a hapten unrelated to the Ir gene control, as in many previous studies. Low responder mice immunized in vivo with Mb bound to an immunogenic carrier, fowl .gamma. globulin (F.gamma.G), produced B cells competent to secrete anti-Mb antibodies in vitro if they received F.gamma.G-specific T cell help. High-responder .times. low responder F1 T cells from Mb-immune mice did not help these primed low responder (H-2k or H-2b) B cells in vitro, even in the presence of various numbers of F1 APC that were demonstrated to be competent to reconstitute the response of spleen cells depleted of APC. Similar results were obtained with B6 .fwdarw. B6D2F1 radiation bone marrow chimeras. Genotypic low responder (H-2b) T cells from these mice helped Mb-primed B6D2F1 B cells plus APC, but did not help syngeneic chimeric H-2b B cells, even in the presence of F1 APC. Ir restriction on APC function was not detected during these in vitro secondary responses. Low responder mice neonatally tolerized to high responder H-2 had competent Mb-specific helper T cells capable of helping high responder but not low responder B cells and APC. Although functional Mb-specific T cells and B cells both exist in low responder mice, the Ir gene defect is a manifestation of the failure of syngeneic collaboration between these 2 cell types. This genetic restriction on the interaction between T cells and B cells is consistent with the additional new finding that Lyb-5-negative B cells are a major participant in this in vitro secondary response because it is this Lyb-5-negative subpopulation of B cells that require genetically restricted help. The b gene defect behaves operationally as a failure of low responder B cells to receive help from any source of Mb-specific T cells, either high responder, low responder or F1. The possible additional role of T cell-APC interactions, either during primary immunization in vivo or in the secondary culture, is discussed.

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