During B cell maturation, mature but still naive B cells migrate from the bone marrow into secondary lymphoid organs and express membrane-bound immunoglobulin of the IgM and IgD isotype on their surface. Only after further activation do the cells enter the so-called germinal center reaction in the lymph follicles, whereby they are able to generate immunoglobulins of all isotypes while retaining the same antigen specificity. Memory B cells, which are generated during this primary immune response, are largely characterized by the expression of CD27 on their surface. When the isotype class is changed, these cells are also called switched memory B cells. Some of these cells recirculate in order to trigger a faster immune response on further contact with the same antigen. Others develop into plasma cells, which only survive for a short time in the blood, unless they migrate to protected niches such as the bone marrow.
However, this germinal center reaction can be disturbed in many sections (e.g. Common variable immunodeficiency (CVID) syndrome or immunosuppressants), as a result of which in some cases only memory B cells with membrane-bound IgM/IgD or even only naive B cells can be detected.
CVID syndrome is a primary immunodeficiency (PID) and comprises a heterogeneous group of patients who have disorders with a wide variety of causes. In summary, however, the patients all suffer from defective antibody production with otherwise largely intact cellular immunity, and show an increased susceptibility to infection. These are usually severe respiratory infections that heal very poorly despite treatment with the usual antibiotics. It is the most common primary immunodeficiency, but is usually only diagnosed in the second to fourth decade of life.
Diagnosis of CVID syndrome in patients over the age of four is based on the following criteria:
- Significant decrease in IgG and IgM or IgA serum concentrations
- Poor or no vaccination response
- Exclusion of other primary immunodeficiencies with associated hypogammaglobulinemia (e.g. combined immunodeficiencies (SCID) or hyper-IgM syndrome) and exclusion of secondary hypogammaglobulinemia (e.g. drugs such as rituximab, malignancies such as multiple myeloma or Waldenström’s disease)