Abstract
Although both marginal zone and follicular B cells produce anti-DNA Abs in murine models of systemic lupus erythematosus, it has been unclear whether these distinct B cell subsets make identical or different Abs. Single-cell analysis demonstrates that the same DNA-reactive B cells can mature to either subset, depending on the hormonal environment. Anti-DNA B cells in estradiol-treated mice become marginal zone cells while identical cells from prolactin-treated mice become follicular cells. The B cell receptor signaling pathway is influenced by hormonal milieu. Thus, hormonal milieu and perhaps B cell receptor signaling, but not antigenic specificity, correlates with the differentiation pathway. These observations have implications for the pathogenesis and treatment of autoimmune disease.
Highlights
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We demonstrate that identical B cells can become either marginal zone (MZ) or follicular cells and that hormonal milieu may be an important determinant of mature B cell differentiation
This study demonstrates that the same B cell can become a MZ B cell in an estrogenic environment and a follicular B cell in a prolactinemic environment
Summary
Female BALB/c mice (8 –14 wk old) from The Jackson Laboratory and 8 –12 wk old female R4A-␥2b BALB/c mice bred in a specific pathogen-free barrier facility at the Albert Einstein College of Medicine and Columbia University were used. Mice were implanted s.c. with 60-day time release pellets containing placebo, 17-estradiol (0.18 mg), or prolactin (6 mg) (Innovative Research of America). Spleen cells were isolated from R4A-␥2b BALB/c mice as well as from BALB/c mice treated with estradiol, prolactin, or placebo. RBC were lysed and splenocytes were stained with the following Abs for subset analysis: CD19 (clone 1D3), CD21 (clone 7G6), CD23 (clone B3B4), AA4.1, and IgG2b (clone R12-3) (for R4A-␥2b BALB/c mice only) and analyzed by flow cytometry (BD Biosciences). The costs of publication of this article were defrayed in part by the payment of page charges. This article must be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact
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