Accelerated Help to B Cells Memory CD 4 T Cells

CD4 T cell help for B cells is critical for effective Ab responses. Although many of the molecules involved in helper functions of naive CD4 T cells have been characterized, much less is known about the helper capabilities of memory CD4 T cells, an important consideration for the design of vaccines that aim to prime protective memory CD4 T cells. In this study, we demonstrate that memory CD4 T cells enable B cells to expand more rapidly and class switch earlier than do primary responding CD4 T cells. This accelerated response does not require large numbers of memory cells, and similar numbers of primary responding cells provide less effective help than do memory cells. However, only memory CD4 T cells that express the B cell follicle homing molecule, CXCR5, are able to accelerate the response, suggesting that the rapidity of the Ab response depends on the ability of CD4 memory T cells to migrate quickly toward B cells. T he basis for immunological memory is that Ag-experienced lymphocytes respond better than their naive counterparts. Although this phenomenon is widely accepted, there is still a paucity of understanding of the mechanisms involved in enhanced memory responses. Memory cells are generated following the initial primary response in which Ag-specific cells first proliferate, differentiate, and then most, but not all, of these cells undergo apoptosis (1). The surviving memory cells differ from naive cells in two main ways. First, there are more Ag-specific cells in the memory as compared with the naive pool (2–4). Second, memory cells can make an effector response more rapidly after stimulation (1, 5). Which of these two factors is important for the improved responses observed upon reactivation is not clearly understood but is an important issue when considering the design of T cell-mediated vaccines. Memory CD4 T cells could provide a protective response to pathogens by helping B cells make a more rapid Ab response (6, 7). That CD4 help is required for primary responding B cells to form germinal centers and produce high-affinity class-switched Ab is well established (8). These signals are supplied via cell surface molecules such as CD40L and ICOS, and by means of soluble molecules such as the cytokines IL-4 and IL-21 (9). The Abs generated by such a response protect the host against invading microorganisms by, for example, neutralizing the invader or improving uptake by phagocytic cells (10). The faster the Ab response …