CD22 × Siglec-G Double-Deficient Mice Have Massively Increased B1 Cell Numbers and Develop Systemic Autoimmunity
- 1 April 2010
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 184 (7), 3618-3627
- https://doi.org/10.4049/jimmunol.0902711
Abstract
CD22 and Siglec-G are inhibitory coreceptors for BCR-mediated signaling. Although CD22-deficient mice show increased calcium signaling in their conventional B2 cells and a quite normal B cell maturation, Siglec-G–deficient mice have increased calcium mobilization just in B1 cells and show a large expansion of the B1 cell population. Neither CD22-deficient, nor Siglec-G–deficient mice on a pure C57BL/6 or BALB/c background, respectively, develop autoimmunity. Using Siglec-G × CD22 double-deficient mice, we addressed whether Siglec-G and CD22 have redundant functions. Siglec-G × CD22 double-deficient mice show elevated calcium responses in both B1 cells and B2 cells, increased serum IgM levels and an enlarged population of B1 cells. The enlargement of B1 cell numbers is even higher than in Siglecg−/− mice. This expansion seems to happen at the expense of B2 cells, which are reduced in absolute cell numbers, but show an activated phenotype. Furthermore, Siglec-G × CD22 double-deficient mice show a diminished immune response to both thymus-dependent and thymus-independent type II Ags. In contrast, B cells from Siglec-G × CD22 double-deficient mice exhibit a hyperproliferative response to stimulation with several TLR ligands. Aged Siglec-G × CD22 double-deficient mice spontaneously develop anti-DNA and antinuclear autoantibodies. These resulted in a moderate form of immune complex glomerulonephritis. These results show that Siglec-G and CD22 have partly compensatory functions and together are crucial in maintaining the B cell tolerance.Keywords
This publication has 48 references indexed in Scilit:
- Developmental Acquisition of the Lyn-CD22-SHP-1 Inhibitory Pathway Promotes B Cell TolerancePublished by The American Association of Immunologists ,2009
- Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humansJCI Insight, 2009
- CD22: an inhibitory enigmaImmunology, 2008
- Control of Toll-like Receptor 7 Expression Is Essential to Restrict Autoimmunity and Dendritic Cell ProliferationImmunity, 2007
- Siglecg Limits the Size of B1a B Cell Lineage by Down-Regulating NFκB ActivationPLOS ONE, 2007
- Siglec-G is a B1 cell–inhibitory receptor that controls expansion and calcium signaling of the B1 cell populationNature Immunology, 2007
- Siglecs and their roles in the immune systemNature Reviews Immunology, 2007
- Identification of chromosome intervals from 129 and C57BL/6 mouse strains linked to the development of systemic lupus erythematosusGenes & Immunity, 2006
- Autoreactive B Cell Responses to RNA-Related Antigens Due to TLR7 Gene DuplicationScience, 2006
- Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand bindingInternational Immunology, 2005