Major histocompatibility complex-restricted self-recognition in responses to trinitrophenyl-ficoll. Adaptive differentiation and self-recognition by B cells.

Abstract

The present study has examined the possibility of TNP-Ficoll-responsive B cells recognize the MHC determinants expressed by the accessory cells with which they interact for the generation of T cell-independent responses to "high" concentrations (10(-2) micrograms/ml) of TNP-Ficoll. In experiments with B cells from normal mice, it was found that MHC homology between the TNP-Ficoll-responsive B cells and accessory cells was not required. Nevertheless, TNP-Ficoll-responsive B cells from both fully allogeneic (A leads to B) and F1 leads to parent radiation bone marrow chimeras were triggered by accessory cells expressing host-type, but not uniquely donor-type, MHC determinants. The MHC gene products responsible for this apparent B cell-accessory restriction were encoded in the left side, i.e., the K and/or I-A region, of H-2. Such genetic restrictions were shown not to be imposed by the residual T cells contaminating the chimeric B cell populations because T cell reconstitution experiments using "unrestricted" F1 T cells from normal mice did not fully overcome the marked preference of the chimeric B cells for accessory cells expressing appropriate (host-type) MHC determinants. To directly determine whether TNP-Ficoll-responsive B cells from fully allogeneic chimeras are unable to recognize and cooperate with syngeneic strain A accessory cells, unfractionated spleen cells from A leads to B chimeras are co-cultured with unfractionated spleen cells from essentially syngeneic normal strain A mice. In such co-cultures, all the accessory cells express strain A MHC determinants, and all T cell requirements would be fulfilled by the T cells present in the normal strain A spleen cell population. After stimulation of the co-cultures with TNP-Ficoll, it was found that virtually all the PFC that had been generated in the co-cultures were derived from the normal B cell population, and essentially none were derived from the chimeric A leads to B B cell population. The failure of the chimeric B cells to be activated in such co-cultures was specifically due to their maturation in a fully allogeneic host environment because TNP-Ficoll-responsive B cells from A leads to (A X B) F1 chimeric mice were successfully triggered in co-cultures with normal spleen cells. These experiments demonstrated that the co-culture conditions did fulfill the MHC restriction requirements for activating TNP-Ficoll-responsive strain A B cells that had matured in a syngeneic or semi-syngeneic differentiation environment, but did not fulfill the MHC restriction requirements for activating TNP-Ficoll-responsive strain A B cells that had matured in a fully allogeneic differentiation environment. Taken together, these results demonstrate that (a) TNP-Ficoll-responsive B cells recognize the MHC determinants expressed by accessory cells, and (b) their MHC specificity is influenced by the MHC haplotype of the host environment in which the B cells had differentiated.

Why Positive Selection?

“…T cells from MHC^ responded to MHC''/x), but chimaeric (axb-^a) cells did not (Doherty & Bennink 1979b). There was even one case where the B cells from an F|--Parent chimaera were unable to use accessory cells expressing the unshared parental MHC type (Singer & Hodes 1982)! By the mid 8O's most immunologists thought that there was something going on in the thymus but no one was entirely sure what.…”

Major histocompatibility complex-restricted self-recognition in responses to trinitrophenyl-Ficoll. A novel cell interaction pathway requiring self-recognition of accessory cell H-2 determinants by both T cells and B cells.

“…In particular, it has recently been shown (15) that B cells from long-term radiation bone marrow chimeras express a requirement for MHC-restricted self-recognition in TI responses to high concentrations of TNPFicoll. These studies did not determine, however, the effects that T cells or soluble T cell products might exert on this B cell function.…”

“…It has recently been demonstrated (12)(13)(14)(15)) that B cells, as well as TH cells, can express requirements for recognition of self-MHC determinants expressed by the accessory cells with which they interact. In particular, it has recently been shown (15) that B cells from long-term radiation bone marrow chimeras express a requirement for MHC-restricted self-recognition in TI responses to high concentrations of TNPFicoll.…”

“…Although the generation of antibody responses to TNP-Ficoll has been most extensively characterized as being independent of a requirement for T cells (15,17), recent studies (23,24) have suggested that under certain experimental conditions, the generation of responses to TNP-Ficoll may be substantially T dependent. To study T cell influences on the activation of TNP-Ficoll-responsive B cells, experiments were carried out to establish conditions in which the T dependence of TNP-Ficoll responses would be clearly apparent.…”

“…It was previously demonstrated (15) that the generation of TI responses to higher concentrations of TNP-Ficoll required MHC-restricted recognition of accessory cells by responding spleen cells from fully allogeneic radiation bone marrow chimeras. To determine whether the TD responses to low concentrations of TNP-Ficoll were similarly restricted, the responses of fully MHC-allogeneic chimeric spleen cell populations were again studied.…”