Radioresistance of B-1 cells from (NZB/NZW) F1 mice: possible role of microRNAs (143.46)

Abstract

Abstract The (NZB/NZW)F1 (B/W) mouse spontaneously develops an autoimmune disease comparable with systemic lupus erythematosus in humans. B-1 cells may be an important cell type in the development of autoimmunity and B-1 cells are distinguished from conventional B cells by developmental origin, surface marker expression and functions, including the production of autoantibodies. Here, we present findings that B-1 cells (but not conventional B cells) from the peritoneal cavity of B/W mice are resistant to 9 Gy of radiation in contrast to B-1 cells derived from C57BL/6 mice. Similar to NZB mice which have a point mutation near the mir-15a/16 loci on chromosome 14 associated with decreased expression of microRNAs miR-15a and miR-16, the B/W are hemizygous for this mutation and also have decreased miR-15a/16. We hypothesized that increased expression of targets of miR-16 in B-1 cells from the B/W mice (such as Bcl-2) could be responsible for the radioresistance observed. Transfection of peritoneal cells from B/W with miR-16 sensitizes the B-1 cells to irradiation. Moreover, 1 hour after irradiation, peritoneal cells from the radiosensitive C57BL/6 also demonstrated an increase in miR-16 expression. Our data indicate a possible role of microRNAs in contributing to the radiation response, with decreased miR-16 associated with radioresistance in B-1 cells derived from the B/W strain. The possible implications of these findings in the pathogenesis of autoimmune disease are under investigation.