B-cell reconstitution and xenoreactive anti-pig natural antibody production in severe combined immunodeficient mice reconstituted with immunocompetent B cells from varying sources

Background. Little is known about the B-cell subsets that produce xenoreactive natural antibodies (NAb). This study was undertaken to investigate the potential role of varying B-cell populations in anti-pig NAb production in mice. Methods. Severe combined immunodeficient (scid) mice were reconstituted with bone marrow or splenic or peritoneal B cells from immunocompetent mice. B-cell reconstitution and anti-pig NAb were evaluated by flow cytometric analysis. Results. Adult marrow failed to reconstitute normal numbers of CD5(+) Bla cells, but fully reconstituted CD5(-) Mac1(-) B2 and CD5(-) Mac1(+) Bib cell populations in scid mice. Recipients of peritoneal B cells showed poor reconstitution of B2 cells, and an overshoot of B1 cells in the peritoneal cavity, Although B2 cells predominate in the adult spleen, splenic B cells from immunocompetent mice preferentially reconstituted B cells, including B1 cells, in the peritoneal cavity, but did not reconstitute splenic B2 cells. Therefore, neither adult marrow, splenocytes nor peritoneal cells can fully reconstitute scid mice with all B-cell subpopulations. Nevertheless, serum anti-pig NAb in mar row-reconstituted mice recovered to normal levels by 3 weeks, and were maintained for at least 30 weeks. Serum NAb in scid mice receiving peritoneal B cells reached normal levels by 4-7 weeks after transfer. However, NAb in sera of acid mice receiving splenic B cells took longer (>25 weeks) to reach normal levels. Conclusions. These results indicate that adult marrow-derived B cells can efficiently produce anti-pig NAb, and that peritoneal B cells have greater NAb-producing ability than splenic B cells or their immediate progeny.