B cells activated via CD40 and IL-4 undergo a division burst but require continued stimulation to maintain division, survival and differentiation.
T cell stimulation of B cell proliferation during T-B collaboration requires membrane-bound stimulatory ligands, such as CD40 ligand and the secretion of soluble cytokines, such as IL-4. Nevertheless, it remains unclear whether T cell contact is required to provoke each consecutive B cell division, or whether B cells divide in a T cell-free burst following the initial stimulation. To test this, naive B cells were cultured with anti-CD40 monoclonal antibody (mAb) and IL-4 and, after various times, these stimuli were removed and the cells re-cultured with or without further stimulation. Following stimulus removal, B cells were able to continue proliferating, with the size of the B cell burst dependent on the strength of the initial anti-CD40 mAb stimulus. Furthermore, in the absence of activating signals from anti-CD40 and/or IL-4, re-cultured B cells died rapidly. In addition, B cells undergoing a stimulus-free division burst could switch to IgG1. Thus, maximal B cell proliferation, differentiation and survival may require continued, although not necessarily consecutive, cognate interactions with T cells. These results suggest that antigen persistence and T cell help are necessary to sustain B cell proliferation and differentiation in vivo.
Rush
J S
JS
Immune Regulation Group, Medical Foundation of the University of Sydney, Centenary Institute of Cancer Medicine and Cell Biology, Sydney, Australia.
Hodgkin
P D
PD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007074:Immunoglobulin G; D023201:CD40 Ligand; D015847:Interleukin-4