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

BMC Immunol. 2015 Nov 4:16:66. doi: 10.1186/s12865-015-0130-z.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • Antigens, CD1d / genetics
  • Antigens, CD1d / metabolism*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • CD5 Antigens / metabolism*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Gene Expression Regulation
  • Homeodomain Proteins / genetics
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin M / immunology
  • Interleukin-10 / biosynthesis*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism


  • Antigens, CD1d
  • CD5 Antigens
  • Homeodomain Proteins
  • Immunoglobulin G
  • Immunoglobulin M
  • RAG-1 protein
  • Interleukin-10