Discs large homolog 1 regulates B cell proliferation and antibody production
Xuejiao Dong  Xinxin Li  Ce Liu  Kun Xu  Yi Shi  Wanli Liu
International Immunology, dxz046, https://doi.org/10.1093/intimm/dxz046
Published: 06 June 2019  Article history
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Abstract
Antibody production is resulted from B cell activation and proliferation upon antigen binding. Discs large homolog 1 (Dlg1), a scaffold protein from membrane-associated guanylate-kinase family, has been shown to regulate the antigen receptor signaling and cell polarity in lymphocytes, however the physiological function of Dlg1 in humoral response is not completely clear. Here we addressed this question using conditional knockout (KO) mouse model with Dlg1 deficiency in different B cell subsets by crossing dlg1fl/fl mice with either mb1cre/+ or aicdacre/+ mice respectively. In both mouse models, we observed that Dlg1 deficiency in B cells (Dlg1-KO B cells) led to obvious hyper-antibody responses upon immunization, the effect of which was more obvious in antigen-recall responses. Mechanistically, we found that Dlg1-KO B cells exhibited hyper-proliferation than wild-type B cells upon antigen stimulation, suggesting that the hyper-antibody responses are likely induced by the hyper-proliferation of Dlg1-KO B cells. Indeed, further studies demonstrated that Dlg1 deficiency in B cells led to the down-regulation of a tumor suppressor, FoxO1. Thus, all these results reveal an unexpected function of Dlg1 in refraining hyper-antibody responses through the inhibition of FoxO1 and thus antigen-binding induced proliferation in B cells.

B cells, B cell receptor, Dlg1, FoxO1, antibody response
Topic: b-lymphocytes antibody formation antibodies mice forkhead box protein o1
Issue Section: ORIGINAL RESEARCH