Altered B-cell subsets and functional B-cell defects in selective IgM deficiency.
Primary selective IgM deficiency (sIgM) is characterized by diminished serum IgM, infections and autoimmunity. Although there is some evidence of B-cell defects the pathogenesis of sIgM is poorly understood. We determined peripheral B-cell subsets and IgM-expression levels in 31 adult sIgM patients by flow cytometry. In a subset of patients B-cell subset alterations and antibody-secreting cells were determined by flow cytometry and ELISpot assay after in vitro differentiation.Patients had significantly increased transitional, decreased IgM only, switched and non-switched memory B cells and decreased membrane IgM-expression levels on memory B-cell subsets compared to healthy controls. A strongly diminished B-cell differentiation and expansion capacity was observed in 5/6 investigated patients. Severely reduced IgM-secreting capacity was detected in 2/6 patients.Taken together, our results show altered B-cell subsets and severe functional B-cell defects in sIgM. This may provide a diagnostic tool and basis for subclassification of patients to study the pathogenetic background.
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Angela
A
Mensen
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Torben
T
Krause
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Leif Gunnar
LG
Hanitsch
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany; Labor Berlin GmbH, Immunology Department, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Christian
C
Meisel
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Maximilian E
ME
Kleint
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.
Hans-Dieter
HD
Volk
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany; Experimental and Clinical Research Center (ECRC), Berlin, Germany; Department of Hematology, Oncology and Tumor Immunology, Charité CVK, Berlin, Germany. Electronic address: il-kang.na@charite.de.
Il-Kang
IK
Na
Institute for Medical Immunology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.
Carmen
C
Scheibenbogen
D000328:Adult; D000906:Antibodies / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D000906:Antibodies; D007075:Immunoglobulin M
Antibody-secreting cells; ELISpot assay; Memory B cells; Primary immunodeficiency; Selective IgM deficiency; Transitional B cells