The Follicular versus Marginal Zone B Lymphocyte Cell Fate Decision Is Regulated by Aiolos, Btk, and CD21

Cancer Center and, Massachusetts General Hospital and, Harvard Medical School, Boston, MA 02129, USA.
Immunity (Impact Factor: 21.56). 06/2001; 14(5):603-15. DOI: 10.1016/S1074-7613(01)00135-2
Source: PubMed


Most splenic B cells in mice that lack Aiolos are mature IgD(hi)IgM(lo) follicular lymphocytes, suggesting that maturation signals delivered via the BCR are enhanced in the absence of Aiolos. The enhanced maturation of follicular B cells is accompanied by the absence of MZ B lymphocytes and the downregulation of CD21 expression in follicular B cells, all of which depend on the generation of signals via Btk, which is in epistasis to Aiolos. The inverse relationship between the strength of BCR signaling and MZ B cell development is supported by an examination of MZ B cells in CD21 null mice. These data support the view that antigens (in contrast to "tonic" signals) drive the development of naive B cells.

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Available from: Katia Georgopoulos, Aug 06, 2014
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    • "Inside the spleen, the bone-marrow emigrant transitional 1 B-lymphocytes differentiate into transitional 2 (T2) B-lymphocytes, most of which then give rise to naïve, mature recirculating follicular B-cells (henceforth referred to as " naïve B-cells " ). Weaker BCR signaling [12] [13], along with Notch2 receptor-Notch2 delta ligand 1 interaction [14] and other factors predestine T2 lymphocytes to become marginal zone-like (MZ-like, also called natural effector) B-cells instead, a sub-group that facilitates a rapid T-independent response to conserved non-protein antigens. MZ-like B-cells are long-lived and self-replenishing. "
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    • "The T2 transitional B cell is thought to be the common precursor for both MZ B and follicular B-2 B cells [4]. Studies on gene-targeted mice have allowed the identification of several MZB cell determinants [5], [6], [7], [8], [9], [10], including effectors of Notch [11], [12], [13], [14], [15], [16], [17] and BCR [18], [19], although their contribution to MZB cell establishment/maintenance remains poorly understood [3], [20]. "
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    • "It has been well documented that weak BCR signaling leads B cells to develop into MZ B cells. For example, mutations of molecules that attenuate BCR signaling, such as Aiolos or CD22, result in an increased number of FO B cells, while MZ B cells are absent [25], [26]. Conversely, deficiencies in molecules that reduce BCR signaling, such as CD21/CR2 deficiency, increase the number of MZ B cells [25]. "
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