Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease

Blood. 2002 Mar 1;99(5):1544-51. doi: 10.1182/blood.v99.5.1544.


Hypogammaglobulinemia is the hallmark of common variable immunodeficiency (CVID) syndrome, a heterogeneous disorder predisposing patients to recurrent bacterial infections. In this study, we investigated the peripheral B-cell compartment of 30 well-characterized CVID patients in comparison to 22 healthy controls. Flow cytometric analysis of peripheral blood lymphocytes revealed a reduction of class-switched CD27(+)IgM(-)IgD(-) memory B cells below 0.4% in 77% of our patients (group I), while this B-cell subpopulation exceeded 0.5% in all healthy donors and in 23% of CVID patients (group II). These results correlate well with the capacity of peripheral blood lymphocytes to produce immunoglobulins in vitro upon stimulation with Staphylococcus aureus Cowan I (SAC) plus interleukin-2 because the production of immunoglobulin G in vitro is entirely dependent on the presence of switched memory B cells. The subdivision of group I into patients with an increased proportion of CD21(-) peripheral B cells (> 20%; group Ia) and patients with normal percentages of CD21(-) B cells (< 20%; group Ib) revealed a significant clustering of patients with splenomegaly and autoimmune cytopenias in group Ia. Based on these observations, we propose a fast and reliable new classification for CVID patients by flow cytometric quantification of class-switched memory and immature B cells in the peripheral blood of patients. Our results point toward defects at various stages of B-cell differentiation in CVID subgroups and support the value of a B-cell-oriented classification principle. A consensus on this new classification system will hopefully provide a tool for rapidly defining homogeneous subgroups of CVID for functional studies and genetic linkage analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD19 / analysis
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Case-Control Studies
  • Common Variable Immunodeficiency / classification*
  • Common Variable Immunodeficiency / immunology*
  • Common Variable Immunodeficiency / pathology
  • Female
  • Flow Cytometry / methods
  • Humans
  • Immunoglobulin Class Switching*
  • Immunoglobulin Isotypes / analysis
  • Immunoglobulin Isotypes / biosynthesis
  • Immunologic Memory
  • Interleukin-2 / pharmacology
  • Male
  • Middle Aged
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / analysis
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology


  • Antigens, CD19
  • Immunoglobulin Isotypes
  • Interleukin-2
  • Tumor Necrosis Factor Receptor Superfamily, Member 7