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The Journal of Immunology, 2003, 170: 686-694.
Copyright © 2003 by The American Association of Immunologists

Intrinsic Differences in the Proliferation of Naive and Memory Human B Cells as a Mechanism for Enhanced Secondary Immune Responses1

Stuart G. Tangye2,*,{dagger}, Danielle T. Avery*, Elissa K. Deenick*,{dagger} and Philip D. Hodgkin3,*,{dagger}

* Immune Regulation Group, Centenary Institute of Cancer Medicine and Cell Biology, Sydney, Australia; and {dagger} University of Sydney, Sydney, Australia

Humoral immune responses elicited after secondary exposure to immunizing Ag are characterized by robust and elevated reactivity of memory B cells that exceed those of naive B cells during the primary response. The mechanism underlying this difference in responsiveness of naive vs memory B cells remains unclear. We have quantitated the response of naive and memory human B cells after in vitro stimulation with T cell-derived stimuli. In response to stimulation with CD40 ligand alone or with IL-10, both IgM-expressing and Ig isotype-switched memory B cells entered their first division 20–30 h earlier than did naive B cells. In contrast, the time spent traversing subsequent divisions was similar. Consistent with previous studies, only memory cells differentiated to CD38+ blasts in a manner that increased with consecutive division number. These differentiated CD38+ B cells divided faster than did CD38- memory B cell blasts. Proliferation of CD40 ligand-stimulated naive B cells as well as both CD38+ and CD38- cells present in cultures of memory B cells was increased by IL-10. In contrast, IL-2 enhanced proliferation of CD38- and CD38+ memory B cell blasts, but not naive cells. Thus, memory B cells possess an intrinsic advantage over naive B cells in both the time to initiate a response and in the division-based rate of effector cell development. These differences help explain the accelerated Ab response exhibited by memory B cells after secondary challenge by an invading pathogen, a hallmark of immunological memory.


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