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A Population of CD19^highCD45R^–/lowCD21^low B Lymphocytes Poised for Spontaneous Secretion of IgG and IgA Antibodies¹

Belén de Andrés^2,*, Isabel Cortegano, Natalia Serrano^*, Borja del Rio^*, Paloma Martín, Pilar Gonzalo^3,*, Miguel A. R. Marcos and María Luisa Gaspar^2,*

^* Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Centro de Biología Molecular S.O., Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, Spain; and Hospital Puerta de Hierro, Instituto Madrileño de la Salud-Universidad Autónoma de Madrid, C/San Martín de Porres, Madrid, Spain

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 CD19^highCD45R^–/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 CD19^highCD45R^–/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 CD19^highCD45R^–/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.

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¹ This work was supported by Instituto de Salud Carlos III (ISCIII PI05/007, ISCIII 03/18) and by Ministerio de Educación y Ciencia (SAF2003-08194). We also acknowledge the intramural funding received by the Centro de Biología Molecular S.O. from the Ramon Areces Foundation and the Banco Santander Central Hispano. P.G., I.C., N.S., B.d.R., and B.d.A. were supported by ISCIII fellowships and by the Ramón y Cajal Program.

² Address correspondence and reprint requests to Dr. Belén de Andrés, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain; E-mail address: bdandres{at}isciii.es or Dr. María Luisa Gaspar, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain; E-mail address: mlgaspar{at}isciii.es

³ Current address: Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, C/Melchor Fernández Almagro, 3, Madrid, Spain.

⁴ Abbreviations used in this paper: FO, follicular; GC, germinal center; MZ, marginal zone; FL, fetal liver; E, gestational day; BM, bone marrow; HPRT, hypoxanthine guanine phosphoribosyl transferase; KSL, c-Kit⁺Sca-1⁺Lin^–.