Identification and analysis of a novel human surface CD5- B lymphocyte subset producing natural antibodies.
The production of "natural" autoantibodies or antibodies, i.e., Ig that bind a variety of self- and/or exogenous Ag and arise independently of known immunization, is though to be a feature of CD5+ B lymphocytes. To determine whether other lymphocyte subsets exist that might be committed to the production of natural antibodies, human peripheral blood B cells were sorted on the basis of surface CD5 expression and differential expression of surface CD45RA (CD5+CD45RAintermediate(int), CD5-CD45RAlow(lo), and CD5-CD45RAhigh(hi)), and analyzed for the type of Ig produced after EBV infection and culture. Like their CD5+ counterparts, most CD5-CD45RAlo B lymphocytes were precursors of cells producing IgM, a major proportion of which displayed the Ag-binding features of natural antibodies. In contrast, CD5-CD45RAhi B cells comprised a high frequency of IgG-producing cell precursors, possibly including memory B lymphocytes. Six of seven IgM mAb generated from sorted CD5-CD45RAlo B cells and three of four IgM mAb from sorted CD5+ B cells were polyreactive, binding with different affinities (Kd, 10(-5) to 10(-8) M) to two or more Ag; the remaining mAb from CD5-CD45RAlo and the mAb from CD5+ B cells each bound to a single Ag (Kd, 10(-7) to 10(-8) M), beta-galactosidase and ssDNA, respectively. CD5-CD45RAlo B cells account for 4.1 +/- 1.2% (mean +/- SD in 11 healthy subjects; CD5+ B cells, 23.3 +/- 6.9%) of total B lymphocytes and display the features of quiescent cells. In a given individual, the number of CD5-CD45RAlo B cells remains constant over time. CD5-CD45RAlo and CD5+ B cells bear surface CD11b and CD14, at densities and/or frequencies apparently higher than those of CD5-CD45RAhi B lymphocytes. Despite their surface CD5- phenotype, CD45RAlo B cells express CD5+ mRNA at levels comparable with those of CD5+ B lymphocytes, whereas CD5-CD45RAhi B cells express only trace amounts of CD5 mRNA. The commitment to natural antibody production and the degree of CD5 mRNA expression suggest that the newly defined CD5-CD45RAlo B cell subset is related to CD5+ B lymphocytes, and may constitute the human homologue of the mouse Ly-1-"sister" B cell population.
Kasaian
M T
MT
Department of Pathology, New York University School of Medicine, New York 10016.
Ikematsu
H
H
Casali
P
P
D000199:Actins / Q000276:immunology; D000917:Antibody Formation; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001667:Binding, Competitive; D018845:CD11 Antigens; D018956:CD5 Antigens; D002460:Cell Line; D002472:Cell Transformation, Viral; D004277:DNA, Single-Stranded / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human; D006649:Histocompatibility Antigens / Q000096:biosynthesis; D006801:Humans; D006822:Hybrid Cells; D007075:Immunoglobulin M / Q000096:biosynthesis; D017493:Leukocyte Common Antigens; D018950:Lipopolysaccharide Receptors; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010767:Phosphorylcholine / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D013745:Tetanus Toxoid / Q000276:immunology; D001616:beta-Galactosidase / Q000276:immunology
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018845:CD11 Antigens; D018956:CD5 Antigens; D004277:DNA, Single-Stranded; D006649:Histocompatibility Antigens; D007075:Immunoglobulin M; D018950:Lipopolysaccharide Receptors; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D013745:Tetanus Toxoid; D010767:Phosphorylcholine; D017493:Leukocyte Common Antigens; D001616:beta-Galactosidase