Cannabinoid receptor 2 positions and retains marginal zone B cells with the splenic marginal zone

Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Journal of Experimental Medicine (Impact Factor: 12.52). 08/2011; 208(10):1941-8. DOI: 10.1084/jem.20111083
Source: PubMed


Specialized B cells residing in the splenic marginal zone (MZ) continuously survey the blood for antigens and are important for immunity to systemic infections. However, the cues that uniquely attract cells to the MZ have not been defined. Previous work demonstrated that mice deficient in cannabinoid receptor 2 (CB2) have decreased numbers of MZ B cells but it has been unclear whether CB2 regulates MZ B cell development or positioning. We show that MZ B cells are highly responsive to the CB2 ligand 2-arachidonylglycerol (2-AG) and that CB2 antagonism rapidly displaces small numbers of MZ B cells to the blood. Antagonism for longer durations depletes MZ B cells from the spleen. In mice deficient in sphingosine-1-phosphate receptor function, CB2 antagonism causes MZ B cell displacement into follicles. Moreover, CB2 overexpression is sufficient to position B cells to the splenic MZ. These findings establish a role for CB2 in guiding B cells to the MZ and in preventing their loss to the blood. As a consequence of their MZ B cell deficiency, CB2-deficient mice have reduced numbers of CD1d-high B cells. We show that CB2 deficiency results in diminished humoral responses to a CD1d-restricted systemic antigen.

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Available from: Yelena Bronevetsky, Apr 16, 2015
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    • "As a result of this computational analysis, an association has now been made in the CL between “mature B cell” and “professional antigen presenting cell” by declaring both cell types are capable of the GO process “antigen processing and presentation of peptide or polysaccharide antigen via MHC class II” (GO:0002504). Other interesting GO associations that we found through term enrichment and that are supported by evidence in the literature include the findings that B-2 B cells are in resting state compared to B-1 B cells [22] by “negative regulation of lymphocyte activation” (GO:0051250), and that marginal zone B cells are capable of “antigen processing and presentation, endogenous lipid antigen via MHC class Ib” (GO:0048006) [23]. Thus one benefit of this approach is the review of the completeness of CL representations. "
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