Abstract
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.
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Acknowledgements
We thank M. Kehry and B. Castle for gifts of reagents used in this study. Supported by the National Health and Medical Research Council of Australia.
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Hasbold, J., Corcoran, L., Tarlinton, D. et al. Evidence from the generation of immunoglobulin G–secreting cells that stochastic mechanisms regulate lymphocyte differentiation. Nat Immunol 5, 55–63 (2004). https://doi.org/10.1038/ni1016
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DOI: https://doi.org/10.1038/ni1016
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