References
Query Results -- Details
MGI Accession ID: MGI:2450515
J Number: J:82017
Other Accession IDs:
Title: The yaa mutation promoting murine lupus causes defective development of marginal zone B cells.
Authors: Amano H; Amano E; Moll T; Marinkovic D; Ibnou-Zekri N; Martinez-Soria E; Semac I; Wirth T; Nitschke L; Izui S
Journal: J Immunol
Volume: 170
Issue: 5
Date: 2003 Mar 1
Year: 2003
Pages: 2293-301
Review Status: Peer Reviewed
Abstract:
The accelerated development of systemic lupus erythematosus (SLE) in BXSB male mice is associated with the presence of an as yet unidentified mutant gene, Yaa (Y-linked autoimmune acceleration). In view of a possible role of marginal zone (MZ) B cells in murine SLE, we have explored whether the expression of the Yaa mutation affects the differentiation of MZ and follicular B cells, thereby implicating the acceleration of the disease. In this study, we show that both BXSB and C57BL/6 Yaa mice, including two different substrains of BXSB Yaa males that are protected from SLE, displayed an impaired development of MZ B cells early in life. Studies in bone marrow chimeras revealed that the loss of MZ B cells resulted from a defect intrinsic to B cells expressing the Yaa mutation. The lack of selective expansion of MZ B cells in diseased BXSB Yaa males strongly argues against a major role of MZ B cells in the generation of pathogenic autoantibodies in the BXSB model of SLE. Furthermore, a comparative analysis with mice deficient in CD22 or expressing an IgM anti-trinitrophenyl/DNA transgene suggests that the hyperreactive phenotype of Yaa B cells, as judged by a markedly increased spontaneous IgM secretion, is likely to contribute to the enhanced maturation toward follicular B cells and the block in the MZ B cell generation.
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