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.
Gommerman
J L
JL
Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
Carroll
M C
MC
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D007108:Immune Tolerance; D007113:Immunity, Innate; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008221:Lymphoid Tissue; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D011951:Receptors, Complement
D011951:Receptors, Complement