B-cell development and function in the absence of the spleen
Splenectomized and asplenic individuals are prone to infections with encapsulated bacteria, mainly caused by Streptococcus pneumoniae. The function of the spleen in the defense against this pathogen is unknown. We used congenitally asplenic Hox11-/- mice to study the function of the spleen for the development of B cells and the immune response to streptococcal polysaccharides. The absence of the spleen is not associated with a defect in the generation of mature B cells, but B-1a cells are severely reduced. Transfer of Hox11-/- fetal liver cells into immunodeficient mice generates B-1a cells thus excluding any intrinsic B cell precursor defect resulting from the absence of Hox11 that could account for this observation. B-1a cells are a major source of natural antibodies which are present in serum without prior infection. Congruent with the absence of B-1a cells, serum IgM levels are reduced in Hox11-/- mice. Splenectomy of wild-type mice demonstrated that the spleen is also important for the survival of B-1a cells, as the majority of peritoneal B-1a cells were lost within one week after removal of the spleen. Hox11-/- and splenectomized mice were immunized with polysaccharides of S. pneumoniae, as B-1a cells play a role in thymus-independent immune responses. In neither case could specific IgM be found, in stark contrast to wild-type or sham-operated control animals. Transfer experiments demonstrated that it was the lack of B-1a cells, rather than the lack of some other B cell population or the absence of the spleen itself, that was responsible for the inability to produce serum IgM to these polysaccharides. Thus, (i) the spleen is not essential for the development of mature B cells and (ii) the spleen plays a crucial role in generating and maintaining the B-1a cell pool. As B-1a cells represent a link between the innate and adaptive immune system their absence may account for the increased susceptibility to bacterial infections associated with asplenia.
Spleen, B-cell, development, asplenia, flowcytometry
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