Early precursors of B lymphocytes I. Rabbit/mouse species differences in the physical properties and surface phenotype of pre-B cells,and in the maturation sequence of early B cells

Cells that possess low levels of internal IgM (or μ chain), with none detectable on the surface, can be identified by immunofluorescence. These “pre-B cells” in rabbits have been characterized and been compared with those of mice, in terms of their ontogeny, physical properties and surface phenotype — partly to reveal features that could be exploited in their purification. The timing of their appearance and their tissue distribution are, in principle, very similar, though they first appear 5-7 days later in the rabbit than in the mouse. Thus, pre-B cells could not be detected in rabbit fetal liver until days 17-20 of gestation; however, their progenitors appeared to be present before that, since, in preliminary experiments, pre-B cells (and subsequently B cells) were generated de novo in closed organ cultures initiated at earlier times. In other respects, pre-B cells are strikingly different in the two species. Rabbit pre-B cells bear detectable surface Fc receptors, not found on these cells in the mouse, and they are almost uniformly large and low in density, whereas mouse pre-B cells are much more heterogeneous and less readily purified. The evidence summarized here that the large pre-B cells identified by immunofluorescence are equivalent to those detected by others in functional assays, amounts to a strong case for their precursor status. In the mouse, their immediate progeny seem to be small pre-B cells which apparently already behave, in functional assays, like the newly developed B cells into which they can rapidly convert. This heterogeneity seen in pre-B cells in mice is apparent instead in the B cells of rabbit lymphopoietic tissues. These vary considerably, not only in size and density, but also in their membrane Ig staining intensity, whereas the B cells in mouse bone marrow are almost exclusively small lymphocytes. In view of their relatively high frequencies in fetal tissues, it is proposed that the conspicuous large, low-density rabbit B cells are intermediates in the development of pre-B cells into small B lymphocytes, and it is therefore concluded that surface Ig and Fc receptors both appear at relatively earlier stages in the rabbit than in the mouse. This conclusion could be tested by culturing these immature B cells after purifying them by exploiting their distinctive properties.