Monoclonal antibodies IAH-CC51, BB6-11C9.6 and B-Ly4 are routinely used to detect CD21 orthologue on the surface of porcine B lymphocytes. Cross-reactive studies show that IAH-CC51 and B-Ly4 recognize only a portion of B cells that are positive for pan-specific BB6-11C9.6. This indicates that CD21 is always present on all mature B cells but can be expressed in at least two differential forms, and these were assigned as CD21(a) and CD21(b). We used IAH-CC51 together with anti-CD2 to define four subpopulations of B cells. Ontogenetic and in vitro culture studies, analysis of cell size, expression of CD11b and class-switched phenotype together with measurement of proliferation and cell death, revealed that these subsets represent distinct populations. Phenotypic and functional features collectively suggest that CD21(b+) B cells are less mature than CD21(b-). The present work is the first to show that distinct subsets of mature B cells can express differential forms of CD21.
- MeSH
- Apoptosis MeSH
- Epitopes immunology MeSH
- Cells, Cultured MeSH
- Antibodies, Monoclonal immunology MeSH
- B-Lymphocyte Subsets classification immunology MeSH
- Swine immunology MeSH
- Receptors, Complement 3d immunology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Increased proportions of naive B cell subset and B cells defined as CD27(neg)CD21(neg)CD38(neg) are frequently found in patients with common variable immunodeficiency (CVID) syndrome. Current methods of polychromatic flow cytometry and PCR-based detection of k deletion excision circles allow for fine definitions and replication history mapping of infrequent B cell subsets. We have analyzed B cells from 48 patients with CVID and 49 healthy controls to examine phenotype, frequency, and proliferation history of naive B cell subsets. Consistent with previous studies, we have described two groups of patients with normal (CVID-21norm) or increased (CVID-21lo) proportions of CD27(neg)CD21(neg)CD38(neg) B cells. Upon further analyses, we found two discrete subpopulations of this subset based on the expression of CD24. The B cell subsets showed a markedly increased proliferation in CVID-21lo patients as compared with healthy controls, suggesting developmental arrest rather than increased bone marrow output. Furthermore, when we analyzed CD21(pos) naive B cells, we found two different subpopulations based on IgM and CD24 expression. They correspond to follicular (FO) I and FO II cells previously described in mice. FO I subset is significantly underrepresented in CVID-21lo patients. A comparison of the replication history of naive B cell subsets in CVID patients and healthy controls implies refined naive B cell developmental scheme, in which human transitional B cells develop into FO II and FO I. We propose that the CD27(neg)CD21(neg)CD38(neg) B cells increased in some of the CVID patients originate from the two FO subsets after loss of CD21 expression.
- MeSH
- CD24 Antigen * biosynthesis genetics MeSH
- Common Variable Immunodeficiency * immunology metabolism pathology MeSH
- Cell Differentiation immunology MeSH
- Child MeSH
- Adult MeSH
- Phenotype MeSH
- Resting Phase, Cell Cycle * immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Lymphocyte Count MeSH
- B-Lymphocyte Subsets immunology classification pathology MeSH
- Cell Proliferation MeSH
- Gene Expression Regulation * immunology MeSH
- Aged MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH