Identification of functional human splenic memory B cells by expression of CD148 and CD27.
Memory B cells isolated from human tonsils are characterized by an activated cell surface phenotype, localization to mucosal epithelium, expression of somatically mutated immunoglobulin (Ig) variable (V) region genes, and a preferential differentiation into plasma cells in vitro. In spleens of both humans and rodents, a subset of memory B cells is believed to reside in the marginal zone of the white pulp. Similar to tonsil-derived memory B cells, splenic marginal zone B cells can be distinguished from naive follicular B cells by a distinct cell surface phenotype and by the presence of somatic mutations in their Ig V region genes. Although differences exist between human naive and memory B cells, no cell surface molecules have been identified that positively identify all memory B cells. In this study, we have examined the expression of the receptor-type protein tyrosine phosphatase CD148 on human B cells. CD148(+) B cells present in human spleen exhibited characteristics typical of memory B cells. These included an activated phenotype, localization to the marginal zone, the expression of somatically mutated Ig V region genes, and the preferential differentiation into plasma cells. In contrast, CD148(-) B cells appeared to be naive B cells due to localization to the mantle zone, the expression of surface antigens typical of unstimulated B cells, and the expression of unmutated Ig V region genes. Interestingly, CD148(+) B cells also coexpressed CD27, whereas CD148(-) B cells were CD27(-). These results identify CD148 and CD27 as markers which positively identify memory B cells present in human spleen. Thus, assessing expression of these molecules may be a convenient way to monitor the development of memory B cell responses in immunocompromised individuals or in vaccine trials.
Tangye
S G
SG
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, USA. tangye@dnax.org
Liu
Y J
YJ
Aversa
G
G
Phillips
J H
JH
de Vries
J E
JE
D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D001483:Base Sequence; D015415:Biomarkers; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D005803:Genes, Immunoglobulin; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000166:cytology* / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D015415:Biomarkers; D017931:DNA Primers; D007135:Immunoglobulin Variable Region; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C486288:PTPRJ protein, human; D017027:Protein Tyrosine Phosphatases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3