Bone marrow cells from young and old New Zealand black mice can reconstitute B lymphocytes in severe combined immunodeficient recipients

Abstract

The formation of B lymphocytes in young New Zealand Black (NZB) mice proceeds at an accelerated rate, resulting in a deficiency of B lineage progenitors in mice of 15 weeks of age and older. Multiple studies have indicated that intrinsic defects in B lineage cells as well as in the hemopoietic microenvironment in which they develop contribute to these cellular abnormalities. To determine whether the B-cell hyperactivity observed in young mice could be observed in a normal environment, bone marrow cells from young (4 weeks or less) NZB donors were transplanted into Severe Combined Immunodeficient (SCID) mice that have a marked deficiency of lymphocytes but an apparently normal hemopoietic microenvironment. Engraftment of donor lymphoid cells can occur without pretransplant conditioning regimens, thus minimizing the chances of transferring microenvironmental elements. Marrow from young NZB donors reconstituted surface IgM-expressing B cells and CFU-B (B-cell colony-forming unit) in the marrow of SCID mouse recipients to levels comparable to that observed with donor NZB.xid marrow. The latter mice carry the xid gene that ameliorates the defects exhibited by B lineage cells of NZB mice. Both the number of surface IgM-expressing B cells and CFU-B were higher in the spleen of SCID mice that received NZB grafts than marrow cells from donor BALB/c or NZB.xid mice. Marrow from young NZB donors also reconstituted Thy-1, L3T4 and Lyt2-expressing cells in the spleen to levels higher than observed with young NZB.xid donor cells. The transplantation of marrow from 6-month-old NZB donors made it possible to test whether B lineage cells were present in that tissue and could mediate reconstitution in the normal SCID environment. Marrow from old NZB donors did reconstitute B cells in the marrow and spleen of SCID recipients. The level of reconstitution was comparable to that mediated by young BALB/c cells and twice that of old NZB.xid donor cells. The absolute number of splenic CFU-B was also higher in recipients of old NZB marrow as compared to young BALB/c cells. Old NZB.xid donor marrow reconstituted splenic Thy-1, L3T4 and Lyt2 T cells to levels less than observed with NZB donor cells. Analysis of serum Ig in recipients of old NZB cells indicated higher levels of total IgM as compared to mice engrafted with NZB.xid cells, and anti-single stranded DNA antibodies were detected.