H-2-linked Ir gene control of VH determinant(s)-specific helper T cells

The fact that helper T cells (Th) recognize antigen in the context of class II MHC antigens is well documented. T cells specific for immunoglobulin (Ig) determinants have been demonstrated as have Th cells that interact with B cells in an idiotype (Id)-restricted manner. It is still controversial whether or not such T cells recognize idiotype in an MHC-restricted fashion. In tackling this problem it is important to have a T cell population selected by the introduction of the Ig bearing the determinant(s) in question and to have both the T cell and B cell populations unbiased by prior intentional exposure to specific exogenous antigen. Thus, the likelihood of such specific antigen-induced interactions is reduced and a clearer view of the Ig-induced interaction can be obtained. With this in mind, we found that T cells from B10.D2 mice immunized with normal BALB/c serum Ig were able to stimulate the response of BALB/c B cells to sheep red blood cells (SRBC) in vitro. H-2-linked Ir gene control was revealed by the ability of these Th cells to recognize BALB/c Ig in association with H-2d (BALB/c) but not H-2b (BALB.B). Through the use of Igh congenic mice, BAB/14 and C.B20, we found the Th cells to be specific for VH (idiotypic) rather than CH (allotypic) determinants; the determinant(s) in question was apparently expressed on some BALB/c anti-SRBC antibodies since these Th cells could help anti-SRBC responses but not anti-horse or anti-burro RBC responses. This conclusion of idiotypic specificity was supported by the fact that these Th cells could be primed with either IgM or IgG from BALB/c serum, one BALB/c anti-SRBC hybridoma protein but not two others or a BALB/c IgM myeloma protein, and by the fact that absorption of the serum on SRBC prior to separation of the Ig for immunization removed the priming ability of that Ig preparation. From the use of B cell mixing experiments, it was determined that the restriction elements of H-2 complex and the appropriate Ig determinants had to be borne on the responding B cells, suggesting that direct T-B collaboration was involved in the Th cell action. Therefore, by priming with normal serum Ig we have generated Th cells which act through direct interaction with responding B cells via a VH determinant(s). In addition, unlike the findings of others using different methods of priming Id-specific Th cells, these Th cells are under H-2-linked Ir gene control.(ABSTRACT TRUNCATED AT 400 WORDS)