Intrafollicular location of marginal zone/CD1dhi B cells is associated with autoimmune pathology in a mouse model of lupus

• Published in: Laboratory investigation Vol. 88; no. 9; pp. 1008 - 1020
• Main Authors: Duan, Biyan, Niu, Haitao, Xu, Zhiwei, Sharpe, Arlene H, Croker, Byron P, Sobel, Eric S, Morel, Laurence
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-09-2008; Nature Publishing Group
• Subjects: Laboratory Medicine; Medicine; Medicine & Public Health; Pathology; research-article; systemic lupus erythematosus; macrophages; B cells; autoimmunity; marginal zone
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.2008.62

Marginal zone (MZ) B cells contain a large number of autoreactive clones and the expansion of this compartment has been associated with autoimmunity. MZ B cells also efficiently transport blood-borne antigen to the follicles where they activate T cells and differentiate into plasma cells. Using the B6.NZM2410.
Sle1.Sle2.Sle3
(B6.TC) model of lupus, we show that the IgM
+
CD1d
hi
/MZ B-cell compartment is expanded, and a large number of them reside inside the follicles. Contrary to the peripheral B-cell subset distribution and their activation status, the intrafollicular location of B6.TC IgM
+
CD1d
hi
/MZ B cells depends on both bone marrow- and stromal-derived factors. Among the factors responsible for this intrafollicular location, we have identified an increased response to CXCL13 by B6.TC MZ B cells and a decreased expression of VCAM-1 on stromal cells in the B6.TC MZ. However, the reduced number of MZ macrophages observed in B6.TC MZs was independent of the IgM
+
CD1d
hi
/B-cell location. B7-2 but not B7-1 deficiency restored IgM
+
CD1d
hi
/MZ B-cell follicular exclusion in B6.TC mice, and it correlated with tolerance to dsDNA and a significant reduction of autoimmune pathology. These results suggest that follicular exclusion of IgM
+
CD1d
hi
/MZ B cells is an important B-cell tolerance mechanism, and that B7-2 signaling is involved in breaching this tolerance checkpoint.