Role of the major histocompatibility complex in T cell activation of B cell subpopulations. lyb-5(+) and lyb-5(-) B cell subpopulations differ in their requirement for major histocompatibility complex-restricted T cell recognition

Abstract

The requirements for T helper (TH) cell recognition of major histocompatibility complex (MHC) determinants expressed by B cells for the activation of unprimed mouse Lyb-5+ and Lyb-5- B cell subpopulations were examined. The generation of primary TH cell-dependent plaque-forming cell responses in vitro microculture required the presence of Lyb-5+ B cells because B cell populations that were deprived, either genetically or serologically, of the Lyb-5+ subpopulation were not activated in these responses. Cell-mixing experiments in which A .times. B .fwdarw. A chimeric TH cells were mixed with purified populations of parental accessory cells and parental B cells demonstrated that the in vitro activation of Lyb-5+ B cells did not require TH cell recognition of B cell MHC determinants, although it did require TH cell recognition of accessory cell MHC determinants. In contrast to the failure of Lyb-5- B cells to be activated in primary TH cell-dependent responses in vitro microculture, isolated populations of Lyb-5- B cells were triggered by TH cells in vivo in short-term adoptive transfer experiments. By the use of A .times. B .fwdarw. A chimeric TH cells and parental strain B adoptive hosts, it was possible in vivo to distinguish genetically restricted TH cell recognition of B cells from genetically restricted TH cell recognition of accessory cells. Similar to the results obtained in vitro, the activation in vivo of unfractionated (Lyb-5+ plus Lyb-5-) B cell populations did not require TH cell recognition of B cell MHC determinants. In the same in vivo responses activation of isolated populations of Lyb-5- B cells did require TH recognition of B cell MHC determinants. The most straight-forward interpretation of these experiments is that TH cell recognition of B cell MHC determinants is required for the activation of Lyb-5- B cells but is not required for the activation of Lyb-5+ B cells. To better understand why TH cell activation of 1 B cell subpopulation is genetically restricted but activation of another subpopulation is not, the response of Lyb-5+ and Lyb-5- B cells to the soluble activating factors present in concanavalin A-induced spleen cell supernates (Con A SN) was examined. Lyb-5- B cells, as opposed to Lyb-5+ B cells, were unable to respond in microculture to the nonspecific TH cell-activating factors present in Con A SN, even though they were able to nonspecifically respond under the same conditions to trinitrophenyl-lipopolysaccharide. The ability of B cell subpopulations to respond to nonspecific soluble T cell factors paralleled their ability to be activated by TH cells in a genetically unrestricted manner. Thus, activation by TH cells of Lyb-5- B cells is MHC restricted but activation of Lyb-5+ B cells is not. Possibly, activation of Lyb-5+ B cells does not require direct interaction with TH cells because they can be activated by soluble activation signals that TH cells secrete.