Evidence from the generation of immunoglobulin G-secreting cells that stochastic mechanisms regulate lymphocyte differentiation.
Naive B lymphocytes undergo isotype switching and develop into immunoglobulin-secreting cells to generate the appropriate class and amount of antibody necessary for effective immunity. Although this seems complex, we report here that the generation of immunoglobulin G-secreting cells from naive precursors is highly predictable. The probabilities of isotype switching and development into secreting cells change with successive cell divisions and interleave independently. Cytokines alter the probability of each differentiation event, while leaving intact their independent assortment. As a result, cellular heterogeneity arises automatically as the cells divide. Stochastic division-linked regulation of heterogeneity challenges the conventional paradigms linking distinct phenotypes to unique combinations of signals and has the potential to simplify our concept of immune complexity considerably.
Hasbold
Jhagvaral
J
Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag Number 6, Newtown, NSW 2042, Australia.
Corcoran
Lynn M
LM
Tarlinton
David M
DM
Tangye
Stuart G
SG
Hodgkin
Philip D
PD
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013269:Stochastic Processes
D007074:Immunoglobulin G; D015848:Interleukin-5; D023201:CD40 Ligand; D015847:Interleukin-4