Exogenous interleukin 7 as a proliferative stimulant of early precursor B cells in mouse bone marrow: efficacy of IL-7 injection, IL-7 infusion and IL-7-anti-IL-7 antibody complexes.

B lymphocyte development in mouse bone marrow (BM) occurs in association with stromal cells which provide essential growth factors, notably interleukin 7 (IL-7). The ability of recombinant IL-7 given systemically by several modes of administration to stimulate proliferation of precursor B cells at successive stages of development was examined. Using immunofluorescence labelling and mitotic arrest, the in vivo proliferative cell dynamics of phenotypically defined B lineage cells was quantitated. Single injections of murine IL-7 (muIL-7) in low and intermediate doses stimulated production both of pro-B cells preceeding the expression of mu heavy chains and large pre-B cells expressing cytoplasmic mu. In contrast, higher doses were not stimulatory. Infusion of muIL-7 from subcutaneous micro-osmotic pumps produced a proliferative wave of TdT+ pro-B cells and pre-B cells followed by elevated numbers of postmitotic small pre-B cells and B cells. Stimulation tended to be followed by secondary oscillations of B lymphopoiesis or an IL-7 refractory state. Pronounced increases in TdT+ pro-B and pre-B cell production resulted from injecting small doses of either muIL-7 or human IL-7 (hIL-7), complexed with anti-IL-7 antibody as carrier protein. The results indicate that exogenous IL-7 at optimal dose can markedly stimulate in vivo B lymphopoiesis from the earliest detectable TdT+ pro-B cell stage onward, and is effective when delivered as a cytokine-anticytokine complex. Copyright 1998 Academic Press Limited.