Cannabinoid receptor 2 is critical for the homing and retention of marginal zone B lineage cells and for efficient T-independent immune responses.

Authors:
Sreemanti Basu
Sreemanti Basu
Blood Research Institute
United States
Avijit Ray, PhD
Avijit Ray, PhD
AbbVie
Senior Scientist II
Immunology, Immuno-oncology, Autoimmunity and Inflammation, Immune tolerance
North Chicago, IL | United States
Bonnie N Dittel
Bonnie N Dittel
Blood Research Institute

J Immunol 2011 Dec 2;187(11):5720-32. Epub 2011 Nov 2.

Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201, USA.

The endocannabinoid system has emerged as an important regulator of immune responses, with the cannabinoid receptor 2 (CB2) and its principle ligand 2-archidonoylglycerol playing a major role. How CB2 regulates B cell functions is not clear, even though they express the highest levels of CB2 among immune cell subsets. In this study, we show that CB2-deficient mice have a significant reduction in the absolute number of marginal zone (MZ) B cells and their immediate precursor, transitional-2 MZ precursor. The loss of MZ lineage cells in CB2(-/-) mice was shown to be B cell intrinsic using bone marrow chimeras and was not due to a developmental or functional defect as determined by B cell phenotype, proliferation, and Ig production. Furthermore, CB2(-/-) B cells were similar to wild type in their apoptosis, cell turnover, and BCR and Notch-2 signaling. We then demonstrated that CB2(-/-) MZ lineage B cells were less efficient at homing to the MZ and that their subsequent retention was also regulated by CB2. CB2(-/-) mice immunized with T-independent Ags produced significantly less Ag-specific IgM. This study demonstrates that CB2 positively regulates T-independent immune responses by controlling the localization and positioning of MZ lineage cells to the MZ.

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http://dx.doi.org/10.4049/jimmunol.1102195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226756PMC

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December 2011
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21 Citations
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