B-CELL RECONSTITUTION AND XENOREACTIVE ANTI-PIG NATURAL ANTIBODY PRODUCTION IN SEVERE COMBINED IMMUNODEFICIENT MICE RECONSTITUTED WITH IMMUNOCOMPETENT B CELLS FROM VARYING SOURCES1

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+ B1a cells, but fully reconstituted CD5- Mac1- B2 and CD5- Mac1+ B1b 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 pre-dominate 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 sub-populations. Nevertheless, serum anti-pig NAb in marrow-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 scid 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.