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

Victoria L. Palmer, Vincent K. Nganga, Mary E. Rothermund, Greg A. Perry, Patrick Swanson

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Article number66
JournalBMC Immunology
Volume16
Issue number1
DOIs
StatePublished - Nov 4 2015

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Interleukin-10
B-Lymphocytes
B-Cell Chronic Lymphocytic Leukemia
Natural Killer T-Cells
T-Lymphocytes
Mental Competency
CD1d Antigen
B-Lymphoid Precursor Cells
Transgenic Mice
Antibody Formation
Immunoglobulin M
Disease Progression
Cell Survival
Leukemia
Down-Regulation
Immunoglobulin G
Lipids
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Cd1d regulates B cell development but not B cell accumulation and IL10 production in mice with pathologic CD5+ B cell expansion. / Palmer, Victoria L.; Nganga, Vincent K.; Rothermund, Mary E.; Perry, Greg A.; Swanson, Patrick.

In: BMC Immunology, Vol. 16, No. 1, 66, 04.11.2015.

Research output: Contribution to journalArticle

Palmer, Victoria L. ; Nganga, Vincent K. ; Rothermund, Mary E. ; Perry, Greg A. ; Swanson, Patrick. / Cd1d regulates B cell development but not B cell accumulation and IL10 production in mice with pathologic CD5+ B cell expansion. In: BMC Immunology. 2015 ; Vol. 16, No. 1.
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AU - Perry, Greg A.

AU - Swanson, Patrick

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