Both CD45Rlow and CD45Rhigh "revertant" CD4 memory T cells provide help for memory B cells

Abstract

During a primary response to thymus dependent antigens, B cells undergo a number of qualitative changes to become memory B cells — processes that require co-stimulatory signals and cytokine help from CD4 T cells. The question of whether distinct, antigen-experienced memory CD4 T cells are subsequently needed to program memory B cells into antibody synthesis has not been clearly resolved.Using an adoptive transfer model in which memory but not naive B cells were stimulated, we evaluated CD4 T cell help using lymphocytes obtained from primed or unprimed thymectomized donors and expressing a naive (CD45R^high) or a memory (CD45R^low) phenotype. Memory B cells, most of which were committed to the IgG1 (Th2) subclass, could be stimulated to produce antibody using help transferred by the CD45R^high naive subset of unprimed donors (slow onset of response), the CD45R^low subset of 7 day primed donors (large, rapid antibody response) or by both the CD45R^low and the CD45R^high "revertant" subsets of 6 month primed donors. We found that antigen primed CD45R^low CD4 T cells reverted (defaulted) with time to a CD45R^high resting state, a change that was prevented by persisting antigen. The evidence suggests that CD4 memory T cells are partitioned into two different functional states (CD45R^high and CD45R^low) and that these determine the characteristics of the memory B cell response in terms of speed, size and longevity.