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: 19.75). 06/2001; 14(5):603-15. DOI: 10.1016/S1074-7613(01)00135-2
Source: PubMed

ABSTRACT 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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    • "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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    • "Strong BCR signaling preferentially commits developing B cells to the FO B cell fate, whereas weak BCR signaling favours the MZ B cell fate [2], [6]. For example, mice deficient in CD22, a negative regulator of BCR signaling, have a reduced number of MZ B cells [45], whereas Aiolos deficient mice have enhanced BCR signaling, and a concomitant reduction in the number of splenic MZ B cells with increased numbers of FO B cells [46], [47]. The Aiolos phenotype can be suppressed by intercrossing the Aiolos-deficient mice with Xid mice, which lack a fully functional BTK tyrosine kinase. "
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