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International Immunology, Vol. 11, No. 2, 279-288, February 1999
© 1999 Japanese Society for Immunology

Type I IFN sets the stringency of B cell repertoire selection in the bone marrow

Rita Vasconcellos1, Deborah Braun1, Antonio Coutinho1,2 and Jocelyne Demengeot1,2

1 CNRS URA 1961, Institut Pasteur, 75724 Paris, France
2 Instituto Gulbenkian de Ciência, 2781 Oeiras, Portugal

Correspondence to: J. Demengeot, Instituto Gulbenkian de Ciência, R. Quinta Grande no 6, 2781 Oeiras, Portugal

Locally produced type I interferon (IFN-I) enhances the sensitivity of bone marrow B cell to IgM receptor ligation. The establishment of B cell repertoires, on the other hand, seems to involve selective processes that are critically dependent on B cell receptor (BCR) ligation. In order to assess the importance of BCR triggering thresholds on the selection of polyclonal unmanipulated B cell populations, we compared VH gene expression and reactivity repertoires in various B cell compartments of wild-type and IFN-I receptor-deficient mice (IFN-I-R–/–). These analyses demonstrate that increased B cell sensitivity to BCR ligation mediated by IFN-I in the bone marrow (BM) has consequences on the stringency of B cell repertoire selection. Thus, the normal counter-selection of both VH7183 gene family expression and multireactivity was impaired among immature BM B cells from mutant mice. Furthermore, as a result of reduced efficiency of BCR ligation-dependent inhibition of terminal differentiation, IFN-I-R–/– animals produce, in BM and thymus, higher numbers of plasma cells secreting antibodies that are more multireactive than wild-type animals. Finally, mutant serum IgM natural antibodies display a more reactive repertoire than controls, a likely reflection of the BM resident plasma cell repertoire. The present observations demonstrate, therefore, that local modulation of BCR triggering thresholds leads to important modifications in the generation and/or selection of normal B cell populations.

Keywords: B cell receptor, B lymphocyte, IFN-I, mice, natural antibodies, repertoire

Transmitting editor: T. Hünig


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