Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone
نویسندگان
چکیده
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.
منابع مشابه
Marginal-zone B cells in the human lymph node and spleen show somatic hypermutations and display clonal expansion.
Splenic marginal-zone B cells, marginal-zone B cells of Peyer's patches in the gut, and nodal marginal-zone B cells (also identified as monocytoid B cells) share a similar morphology and immunophenotype. These cells likely represent a distinct subset of B cells in humans and rodents, but their precise ontogenetic relationship as well as their origin from B cells of the germinal center is still ...
متن کاملMarginal zone lymphomas with plasmacytic differentiation and related disorders.
Marginal zone lymphomas of all types (nodal, splenic, and extranodal mucosa-associated lymphoid tissue [MALT]) may show plasmacytic differentiation. Distinguishing marginal zone lymphomas from other small B-cell lymphomas with plasmacytic differentiation, especially lymphoplasmacytic lymphoma, or from plasma cell neoplasms may be challenging. Marginal zone lymphomas with plasmacytic differentia...
متن کاملCotargeting BCL-2 and BCL-XL for maximal efficacy in ALL.
1. Spina V, Khiabanian H, Messina M, et al. The genetics of nodal marginal zone lymphoma. Blood. 2016; 128(10):1362-1373. 2. Thieblemont C, Molina T, Davi F. Optimizing therapy for nodal marginal zone lymphoma. Blood. 2016; 127(17):2064-2071. 3. Kanellis G, Roncador G, Arribas A, et al. Identification of MNDA as a new marker for nodal marginal zone lymphoma. Leukemia. 2009;23(10): 1847-1857. 4....
متن کاملBCR and TLR signaling pathways are recurrently targeted by genetic changes in splenic marginal zone lymphomas.
The genetics and pathogenesis of splenic marginal zone lymphoma are poorly understood. The lymphoma lacks chromosome translocation, and approximately 30% of cases are featured by 7q deletion, but the gene targeted by the deletion is unknown. A recent study showed inactivation of A20, a "global" NF-κB negative regulator, in 1 of 12 splenic marginal zone lymphomas. To investigate further whether ...
متن کامل