Characterization of Lymphocyte Subsets in Patients with common variable immunodeficiency reveals subsets of naive human B cells marked by CD24 expression
| Authors | |
|---|---|
| Year of publication | 2010 |
| Type | Article in Periodical |
| Magazine / Source | Journal of immunology |
| MU Faculty or unit | |
| Citation | |
| Doi | http://dx.doi.org/10.4049/jimmunol.0903876 |
| Field | Immunology |
| Keywords | B cells; flow cytometry; CVID |
| Description | Increased proportions of naive B cell subset and B cells defined as CD27negCD21negCD38neg 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 CD27negCD21negCD38neg 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 CD21pos 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 CD27negCD21negCD38neg B cells increased in some of the CVID patients originate from the two FO subsets after loss of CD21 expression. |