Intrinsic differences in the proliferation of naive and memory human B cells as a mechanism for enhanced secondary immune responses

SG Tangye, DT Avery, EK Deenick… - The Journal of …, 2003 - journals.aai.org
The Journal of Immunology, 2003journals.aai.org
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 …
Abstract
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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