Intrinsic differences in the proliferation of naive and memory human B cells as a mechanism for enhanced secondary immune responses.
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.
Tangye
Stuart G
SG
Immune Regulation Group, Centenary Institute of Cancer Medicine and Cell Biology, Sydney, Australia. s.tangye@centenary.usyd.edu.au
Avery
Danielle T
DT
Deenick
Elissa K
EK
Hodgkin
Philip D
PD
D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013997:Time Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
D015703:Antigens, CD; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D001973:Bromodeoxyuridine