engleski

Impaired development of B1a cells in NKG2D- deficient mice

B1 cells, the predominant lymphocytes in the peritoneal and pleural cavities, are „innate-like“ B cells which produce natural polyclonal IgM antibodies and therefore are the first line of defense against bacterial infections. Much is still unknown about factors controlling the formation of B1 cells. Previously we found that NKG2D deficient mice have altered lymphocyte populations. In this study we investigated the role of the NKG2D receptor in the establishment and maintenance of the B cell pool. Flow cytometric analysis revealed that NKG2D-deficient mice have greatly reduced numbers of B1a cells in the peritoneal and pleural cavities. In correlation with this finding, we also found reduced levels of IgM in both cavities, yet serum IgM levels were not affected. We found no differences in formation of germinal centres upon TNP-KLH immunization. Experiments using bone marrow chimeras reconstituted with mixed fetal liver cells of WT and NKG2D-deficient mice showed that in B1a compartment in the peritoneal cavity contains relatively more wild type cells, whereas B2 cells originated more from knock-out donor cells in all investigated organs. The reduced number of B1a cells in NKG2D-/- mice had also functional consequences, as peritoneal infection with Francisella novicida resulted in a higher bacterial load in various organs. We also found that upon induction of sepsis with the caecal ligation and puncture model, knock-out mice were much more susceptible to peritonitis and had a higher mortality rate. Here we report that NKG2D deficiency results in impaired B cell development which leads to lower numbers of B1a cells in the peritoneal cavity, subsequently leading to lower IgM levels. NKG2D-deficient mice are therefore more susceptible to bacterial infections because of the lower levels of natural antibodies.

B1a cells; NKG2D; Francisella novicida

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