Negative selection of B lymphocytes: a novel role for innate immunity

Gommerman, Jennifer L.
Carroll, Michael C.

Authors' addresses Jennifer L. Gommerman¹, Michael C. Carroll^1,2, ¹The Center for Blood Research, Harvard Medical School, Boston, Massachusetts, USA. ²The Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

Correspondence to: Michael C. Carroll; Center for Blood Research; Harvard Medical School; 200 Longwood Avenue; Boston MA 02115; USA; Fax: 1 617 432 2108; e-mail: [email protected]

Acknowledgements We thank members of the lab who contributed to the work described in the review. Also, we thank Drs A. Rolink and E. Palmer for critical review of the manuscript. The research was supported by grants from the National Institute of Health to M.C.C.J.L.G. is supported by a fellowship from the Medical Research Council of Canada.

Immunological Reviews 173:p 120-130, February 2000.

Summary:

Evidence has accumulated that strongly supports a role for innate immunity in B-cell tolerance. Specific recognition proteins, such as natural antibody and collectins, are present in serum that identify highly conserved self-antigens such as nuclear proteins and activate the classical pathway of complement. The direct localization of these types of antigens to the lymphoid compartment in a complement-receptor-dependent manner provides a mechanism to deal with immature, self-reactive B cells developing daily in the bone marrow. Since it would be disadvantageous for the organism to maintain self-reactive B cells, which cross-react with microbial antigens, the innate immune system provides an efficient pathway for their removal or silencing. A possible outcome of a breakdown in this pathway, as found in individuals bearing natural deficiencies in complement C1q or C4, is autoimmunity such as systemic lupus erythematosus.