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BCR-dependent lineage plasticity in mature B cells

Robin Graf,J. Seagal,K. Otipoby,K. Lam,Salah Ayoub,Baochun Zhang,S. Sander,V. T. Chu,K. Rajewsky

Published 2019 in Science

ABSTRACT

B1 or B2? The BCR decides Immunological B cells are generally divided into two major subsets. B2 cells generate specific antibodies against foreign antigens in secondary lymphoid organs. B1 cells, found predominantly in the peritoneal and pleural cavities, instead produce “natural” antibodies as part of the innate immune system. Two models to explain this split exist: the “lineage model,” wherein both subsets have distinct progenitors, and the “selection model,” in which fates are directed by different B cell antigen receptors (BCRs). Graf et al. provide support for the selection model using a transgenic system in which BCR specificities can be changed. Mature B2 cells differentiated into functional B1 cells when a self-reactive B1 BCR was swapped in, in the absence of B1 lineage precommitment. Science, this issue p. 748 Mature B cells show B cell antigen receptor–dependent ability to differentiate into different immunological cell types. B2 cells engage in classical antibody responses, whereas B1 cells are considered carriers of innate immunity, biased toward recognizing epitopes present on the surfaces of common pathogens and self antigens. To explore the role of B cell antigen receptor (BCR) specificity in driving B1 cell differentiation, we developed a transgenic system allowing us to change BCR specificity in B cells in an inducible and programmed manner. Mature B2 cells differentiated into bona fide B1 cells upon acquisition of a B1 cell–typical self-reactive BCR through a phase of proliferative expansion. Thus, B2 cells have B1 cell differentiation potential in addition to their classical capacity to differentiate into memory and plasma cells, and B1 differentiation can be instructed by BCR-mediated self-reactivity, in the absence of B1-lineage precommitment.

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