B cell heterogeneity. I. A study of B cell subpopulations involved in the reconstitution of an X-linked immune defect of B cell differentiation.

Male (CBA/N × BALB/c) F1 hybrid mice cannot mount humoral immune responses to thymus-dependent (T.D.) or thymus-independent (T.I.) phosphorylcholine (PC) antigens and to trinitrophenyl (TNP)-AECM-Ficoll and TNP-AECM-dextran. Transplantation of spleen, bone marrow, or neonatal liver cells from BALB/c mice can restore responsiveness to these antigens. Engraftment of spleen and bone marrow cells occurs in unirradiated NBF1 hosts, whereas restoration of PFC responses by neonatal liver cells requires a sublethally irradiated NBF1 recipient. Reconstitution experiments demonstrated that the spleen contains T.D. and T.I. B cell precursors that can respond immediately to antigenic challenge, although the bone marrow contains only mature T.D. B cells and immature cells (progenitor cells) which will restore T.I. responses 2 weeks after transplantation. Neonatal liver cells contain only immature progenitor cells which, after 1 to 2 weeks in the NBF1 recipient, become antigen-reactive cells. In contrast to anti-TNP PFC responses, which are fully restored in all NBF1 recipients of BALB/c neonatal cells, only a fraction of NBF1 mice gain responsiveness to PC antigens. The frequency of successful reconstitutions of T.D. anti-PC PFC responses was higher than T.I. anti-PC responses. Idiotypic analysis in the reconstituted recipients demonstrated that H8 and non-H8 anti-PC PFC were being generated. Evidence is presented to indicate that the reconstitution with neonatal liver cells functionally resembles a limiting dilution assay for immature PC-specific progenitor cells, which include both H8 and non-H8 idiotype specificities in T.D. and T.I. anti-PC responses.