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.