Cd1d regulates B cell development but not B cell accumulation and IL10 production in mice with pathologic CD5+ B cell expansion. (December 2015)

• Record Type: Journal Article
• Authors: Palmer, Victoria; Nganga, Vincent; Rothermund, Mary; Perry, Greg; Swanson, Patrick
• Is Part Of: BMC immunology. Volume 16:Number 1(2015)
• Page Start: 1
• Page End: 12
• Publication Date: 2015-12
• Subjects: CD1d -- CLL -- B10 B cell -- Natural killer T cell -- CD5 -- TCL1; Immunology -- Periodicals; Immune System -- Periodicals; Immunity -- Periodicals; Immune System Diseases -- Periodicals; Immunologic Techniques -- Periodicals; 616.07905
• DOI: 10.1186/s12865-015-0130-z
• Languages: English
• ISSNs: 1471-2172

Abstract

Abstract Background CD1d is a widely expressed lipid antigen presenting molecule required for CD1d-restricted invariant natural killer T (iNKT) cell development. Elevated CD1d expression is detected in CD5+ IL10-producing B cells, called B10 B cells, and is correlated with poorer prognosis in chronic lymphocytic leukemia (CLL), a CD5+ B cell malignancy with B10-like functional properties. Whether CD1d expression regulates CD5+ B cell accumulation, IL10 competence, and antibody production in naïve mice with pathologic CD5+ B cell expansion remains untested. Results Using three different transgenic mouse models of benign or leukemic CD5+ B cell expansion, we found that CD1d was differentially expressed on CD5+ B cells between the three models, but loss of CD1d expression had no effect on CD5+ B cell abundance or inducible IL10 expression in any of the models. Interestingly, in the CLL-prone Eμ-TCL1 model, loss of CD1d expression suppressed spontaneous IgG (but not IgM) production, whereas in the dnRAG1xEμ-TCL1 (DTG) model of accelerated CLL, loss of CD1d expression was associated with elevated numbers of splenic CD4+ and CD8+ T cells and an inverted CD4+ :CD8+ T cell ratio. Unexpectedly, before leukemia onset, all three transgenic CD1d-deficient mouse strains had fewer splenic transitional B cells than their CD1d- proficient counterparts. Conclusions The results show that CD1d expression and iNKT cells are dispensable for the development, accumulation, or IL10 competence of CD5+ B cells in mice prone to benign or leukemic CLL-like B cell expansion, but reveal a novel role for iNKT cells in supporting B cell progression through the transitional stage of development in these animals. These results suggest CD1d-directed therapies to target CLL could be evaded by downregulating CD1d expression with little effect on continued leukemic CD5+ B cell survival. The data also imply that iNKT cells help restrain pro-leukemic CD8+ T cell expansion in CLL, potentially explaining a reported correlation in human CLL between disease progression, the loss of NKT cells, and a paradoxical increase in CD8+ T cells.