Dynamics of the splenic innate-like CD19⁺CD45Rlo cell population from adult mice in homeostatic and activated conditions.

In the adult spleen, CD19⁺CD45R(-/lo) (19⁺45R(lo)) lymphocytes of embryonic origin exist as a distinct population to that of the conventional B cell lineage. These cells display a plasmablast phenotype, and they spontaneously secrete IgG1 and IgA, whereas the bone marrow population of 19⁺45R(lo) cells contains B1 progenitors. In this study, we show that 19⁺45R(lo) cells are also present in Peyer's patches and in the spleen throughout the life span of wild-type mice, beginning at postnatal day 7. Although this population is heterogeneous, the surface phenotype of most of these cells distinguishes them from follicular, transitional, marginal zone, and B1 cells. In CBA/CaHN mice, few 19⁺45R(lo) cells were detected at postnatal day 7, and none was observed in the adult spleen. Splenic 19⁺45R(lo) cells exhibited homeostatic BrdU uptake in vivo and actively transcribed cell cycle genes. When transferred to immunodeficient RAG2⁻/⁻γchain⁻/⁻ recipient mice, 19⁺45R(lo) cells survived and differentiated into IgG1- and IgA-plasma cells. Moreover, in vitro stimulation of splenic 19⁺45R(lo) cells with LPS, CpG, BAFF/IL4, and CD40/IL4 induced cell proliferation, IgG1/IgA secretion and the release of IL-10, suggesting a potential immunoregulatory role for this subset of innate-like B cells.

The first 3 days of B-cell development in the mouse embryo.

B-lineage-committed cells are believed to arise in the liver of mouse embryos at 14 days after coitus (dpc). However, pre-B-specific gene transcripts and DJH gene rearrangements have been detected in earlier, midgestation embryos. We describe here a population of c-kit(+)AA4.1(+)CD19(+)Pax5(+) cells present in the aorta-gonad-mesonephros (AGM) area and in the livers of 11-dpc mouse embryos. In contrast to multipotent c-kit(+)AA4.1(+)CD19(-) hematopoietic stem cells (HSCs), these c-kit(+)AA4.1(+)CD19(+) progenitors differentiated only to B-lineage cells in vitro. We propose that mouse embryonic B lymphopoiesis starts earlier than previously thought, at 10 to 11 dpc, both in liver and extra-liver hematopoietic sites. The B-cell differentiation program is not delayed with respect to the emerging lymphohematopoiesis events in the midgestation mouse embryo (8-9 dpc).