Accumulation of splenic B1a cells with potent antigen-presenting capability in NZM2410 lupus-prone mice

Abstract

Objective. In order to shed light on the role of splenic B1 cells in disease pathogenesis in lupus-prone mice, this study was undertaken to determine how efficiently these cells can serve as antigen-presenting cells (APC) and to ascertain which mnrine lupus susceptibility loci dictate the expansion of these cells.Methods. Spleens and peritoneal cavities (PerC) of NZM2410 lupus-prone mice, as well as of control B6 and New Zealand white mice, were examined for the prevalence, surface phenotype, and possible anatomic location of B1 cells. The antigen-presenting ability of fluorescence-sorted splenic Bla cells was assessed. Levels of B1 cells were examined in B6 mice congenic for 4 different lupus susceptibility intervals.Results. NZM2410 lupus mice showed an expansion of splenic and PerC Bla cells at all ages. These cells expressed high levels of B71, B72, CD24, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1, and had the functional capability to serve as APC. Among the lupus susceptibility intervals studied, Sle2, but not Skl, Sle3, or the H2 locus, affected the expansion of BI cells.Conclusion. These findings raise the possibility that the genetically determined expansion of splenic Bla cells in lupus-prone mice might contribute to disease

Human innate B cells: a link between host defense and autoimmunity?

“…In patients with SLE, the balance between these interactions would be shifted in the direction of autoimmunity either due to intrinsic B cell defects, abnormal T cell responses or both [123,124] and MZ B cells stimulated by T cells could enter the GC reaction [125]. Of particular interest in this respect is the expansion of αβ DN T cells observed in murine and human lupus and in patients with the autoimmune lymphoproliferative syndrome (ALPS), who have a very high incidence of autoantibody-mediated cytopenias [119,126,127,128,129,130,131].…”

Dominant NZB contributions to lupus in the (SWR×NZB)F1 model

“…More recently, congenic dissection studies have also shed light on the respective roles of these loci in disease pathogenesis. [21][22][23][24][25][26][27] The (SWR × NZB)F1 (or SNF1) hybrid model is another strain which develops lupus nephritis that is clinically very similar (in onset, severity, female bias, and pathology) to the BWF1 disease. Studies in this model have clearly demonstrated the relative contributions of antigen-specific, and antigen non-specific modalities of T cell: B cell cross-talk in orchestrating disease, as reviewed.…”

Deficiency of type I interferon contributes to Sle2‐associated component lupus phenotypes

“…In particular, expanded B1a cells constitute a prominent feature in these mice, particularly during maturation (28,29). To ascertain if IFN-I had any effect on the occurrence of these B cells, B6 and B6.Sle2 mice treated with IFN-I, anti-IFN-I antibodies, or placebo were examined for the relative frequencies of peritoneal and splenic B1a, B1b, and B2 cells.…”

“…The NZM2410 Sle2 interval was inherited in part from NZW, and in part from NZB. The immunologic phenotypes of the B6.Sle2 congenic strain have previously been reported (26)(27)(28)(29). B6.Sle1 NZM2410/NZM2410 (simply referred to as B6.Sle1) mice are congenic homozygotes for the 95% confidence interval flanking Sle1, derived from the NZM2410 strain, as previously described (27).…”

“…When bred onto the "normal" C57BL/6 (B6) background, this locus was associated with generalized B cell hyperactivity, marked by polyclonal/polyreactive hypergammaglobulinemia, a reduced number of mature B cells in the bone marrow, and elevated splenic and peritoneal B1a cells. Despite these B cell phenotypes, full-blown lupus glomerulonephritis did not develop in the congenic mice (26)(27)(28)(29).…”