A Population of CD19highCD45R−/lowCD21low B Lymphocytes Poised for Spontaneous Secretion of IgG and IgA Antibodies

Abstract

Ab responses to selected Ags are produced by discrete B cell populations whose presence and functional relevance vary along the ontogeny. The earliest B lineage-restricted precursors in gestational day 11 mouse embryos display the CD19+CD45R/B220− phenotype. Phenotypically identical cells persist throughout gestation and in postnatal life, in parallel to the later-arising, CD19+CD45R+ B cells. Very early after birth, the CD19+CD45R− B cell subset included high frequencies of spontaneously Ig-secreting cells. In the adult spleen, a small subset of CD19highCD45R−/lowIgM+/−IgD−CD21/Cr2−/low cells, which was detected in perifollicular areas, displayed genetic and phenotypical traits of highly differentiated B cells, and was enriched in IgG- and IgA-secreting plasma cells. In vitro differentiation and in vivo adoptive transfer experiments of multipotent hemopoietic progenitors revealed that these CD19highCD45R−/low B cells were preferentially regenerated by embryo-, but not by adult bone marrow-, derived progenitors, except when the latter were inoculated into newborn mice. Both the early ontogenical emergence and the natural production of serum Igs, are shared features of this CD19highCD45R−/low B cell population with innate-like B lymphocytes such as B1 and marginal zone B cells, and suggest that the new population might be related to that category.

Dynamics of the Splenic Innate-like CD19+CD45Rlo Cell Population from Adult Mice in Homeostatic and Activated Conditions

“…CBA/N mice bearing the btk mutation exhibited a 30-50% reduction in FO cells and a severe reduction of B1a and B1b subpopulations. We confirmed that btk-deficient CBA/N mice contained very few 19 + 45R lo cells in these structures, suggesting a strong btk dependency of these cells, as reported elsewhere (23). However, 19 + 45R lo cells did not express CD11b or CD5 (Fig.…”

“…In the spleen, this population could be clearly distinguished from the Transitional cell subsets, conventional MB cells, ABC, and B1 cells. These observations, together with our previous confocal microscopy findings demonstrating a perifollicular distribution of 19 + 45R lo cells (23), suggest that these cells represent a B cell subset of embryonic origin.…”

“…We previously reported that 19 + 45R lo cells of embryonic origin are present in the spleen of infant mice (23). In this study, we traced these cells to different lymphoid locations beginning at postnatal day (PD) 7.…”

“…We previously found that these cells were of embryonic origin, spontaneously incorporated thymidine, and expressed the nuclear Ag Ki67 (23). In this study, we determined their proliferative status in vivo by analyzing BrdU incorporation after continuous i.p.…”

“…In mouse bone marrow (BM), the CD19 + CD45R 2/lo (19 + 45R lo ) cell population (hereafter referred to as 19 + 45R lo ) is an immature population containing B1 progenitors (20)(21)(22). We previously described the presence of 19 + 45R lo cells of embryonic origin in the spleen of juvenile and adult mice (23). These cells have a singular phenotype (CD5 2 CD11b 2 CD21 lo CD23 2 IgD 2 ) with bimodal expression of IgM and spontaneously release IgG1 and IgA.…”