In vitro and in vivo allogeneic effects: differential modulation of B cell subpopulations.

Abstract

We examined the sensitivity of primary TD and TI responses to allogeneic effects and found that primary TD responsive B cells were very sensitive to negative allogeneic effects elicited in vitro. The primary TI-2 responses, on the other hand, were not suppressed but rather enhanced twofold to threefold under the same culture conditions. Thus, primary B cell subsets resemble their IgG memory counterparts (1) in their differential sensitivity to allogeneic T cells. The ability of in vivo induced allogeneic effects of modulate antibody responses was studied using chronic graft-vs-host reaction (GVH) as a model. F1 mice immunized with TD (TNP-KLH, TNP-sheep-gamma-globulin) antigens shortly after GVH induction had reduced IgM and IgG primary responses. In contrast, the primary response to TNP-Ficoll was enhanced and included a large number of primary IgG PFC. Furthermore, mice undergoing chronic GVH were incapable of developing long-term memory after immunization with a TD antigen (TNP-KLH), as determined by secondary in vitro challenges with either TD or TI antigens. These mice retained helper T cells, indicating a failure of memory development in the B cell compartment. These studies suggest that the secondary TD- and TI-responding precursors (B2 gamma and B1 gamma, respectively) are probably both derived from primary B2 precursors (which are very sensitive to negative allogeneic effects). The maturation of the B1 memory population may thus be linked to increased resistance to allosuppression.