title: Intact B cell tolerance in the absence of the first component of the classical complement pathway.
abstract: A critical role for complement in the regulation of self tolerance has been proposed to explain the strong association between complement deficiency and autoimmunity. To elucidate the role of the classical pathway of complement in the maintenance of B cell tolerance, C1q-deficient (C1qa-/-) mice were bred with anti-hen egg lysozyme (HEL) immunoglobulin (Ig(HEL)) and soluble HEL (sHEL) transgenic mice. B cell tolerance was intact in C1qa-/- mice. In vivo, double-transgenic (Ig(HEL)/sHEL) C1qa-/- and wild-type control mice down-regulated surface immunoglobulin expression on splenocytes and equivalent numbers of HEL-binding B cells accumulated in the periphery. Maturation of B cells, evidenced by CD21 expression, was retarded to the same extent and at a similar time point. The frequency of anti-HEL-producing plasma cells and serum levels of anti-HEL immunoglobulin were comparably reduced in control and C1qa-/- double-transgenic mice compared to control Ig(HEL) and C1qa-/- Ig(HEL) mice. Furthermore, splenocytes from double-transgenic C1qa-/- or wild-type mice did not modulate intracellular calcium levels after stimulation with HEL in vitro. These data demonstrate that a stable form of B cell anergy persists in the periphery of C1qa-/- mice, suggesting that activation of the classical pathway by C1q is not essential for the maintenance of B cell tolerance in this transgenic model.
authors.affiliation: Rheumatology Section, Division of Medicine, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London, GB, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Cutler
authors.forename: R J
authors.initials: RJ
authors.lastname: Cornall
authors.forename: H
authors.initials: H
authors.lastname: Ferry
authors.forename: A P
authors.initials: AP
authors.lastname: Manderson
authors.forename: M
authors.initials: M
authors.lastname: Botto
authors.forename: M J
authors.initials: MJ
authors.lastname: Walport
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D017635:Clonal Anergy; D015922:Complement C1q / Q000235:genetics*; D015935:Complement C4b / Q000276:immunology; D003171:Complement Pathway, Classical; D007136:Immunoglobulins / Q000276:immunology; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D017634:Self Tolerance; D013154:Spleen / Q000276:immunology
chemical_list: D001324:Autoantigens; D007136:Immunoglobulins; D015922:Complement C1q; D015935:Complement C4b; C421864:hen egg lysozyme; D009113:Muramidase; D002118:Calcium