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

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 (CD45Rhigh) or a memory (CD45Rlow) 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 CD45Rhigh naive subset of unprimed donors (slow onset of response), the CD45Rlow subset of 7 day primed donors (large, rapid antibody response) or by both the CD45Rlow and the CD45Rhigh "revertant" subsets of 6 month primed donors. We found that antigen primed CD45Rlow CD4 T cells reverted (defaulted) with time to a CD45Rhigh 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 (CD45Rhigh and CD45Rlow) and that these determine the characteristics of the memory B cell response in terms of speed, size and longevity.