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

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.