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Journal of Clinical Immunology

, Volume 34, Issue 6, pp 615–626 | Cite as

Ill-Defined Germinal Centers and Severely Reduced Plasma Cells are Histological Hallmarks of Lymphadenopathy in Patients with Common Variable Immunodeficiency

  • Susanne Unger
  • Maximilian Seidl
  • Annette Schmitt-Graeff
  • Joachim Böhm
  • Klaudia Schrenk
  • Claudia Wehr
  • Sigune Goldacker
  • Ruth Dräger
  • Barbara C. Gärtner
  • Paul Fisch
  • Martin Werner
  • Klaus WarnatzEmail author
Original Research
First Online:

Abstract

Given the severely reduced numbers of circulating class-switched memory B cells and plasmablasts in patients with common variable immunodeficiency (CVID) the germinal center (GC) reaction as the source of both populations is expected to be disturbed in many CVID patients. Therefore immunohistochemical studies were performed on lymph node (LN) biopsies from ten CVID patients with benign lymphoproliferation. According to the Sander classification the majority of patients presented with reactive lymphoid hyperplasia (7/10), 6/10 showed granulomatous inflammation. All cases showed some normal GCs but in 9/10 these concurred to a varying degree with hyperplastic, ill-defined GCs in the same LN. The percentage of ill-defined GCs correlated significantly with the percentage of circulating CD21low B cells suggesting a common origin of both immune reactions. In 9/10 CVID LNs significantly higher numbers of infiltrating CD8+ T cells were found in GCs of CVID patients compared to controls, but no HHV-8 and only in 2/10 LNs EBV infection was detected. Class switched plasma cells (PCs) were severely reduced in 8/10 LNs and if present, rarely found in the medulla of the LN. Based on the presence of large GCs in all examined patients, the reduction of circulating memory B cells and PCs points towards a failure of GC output rather than GC formation in CVID patients with lymphadenopathy.

Keywords

Common variable immunodeficiency plasma cell CD8 T cell germinal center granuloma histology 
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Notes

Acknowledgments

We would like to thank Mrs. Weinhold for excellent technical assistance.

Supplementary material

10875_2014_52_MOESM1_ESM.docx (15 kb)
Table S1 (DOCX 15 kb)
10875_2014_52_MOESM2_ESM.docx (15 kb)
Table S2 (DOCX 14 kb)
10875_2014_52_MOESM3_ESM.docx (16 kb)
Table S3 (DOCX 15 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Susanne Unger
    • 1
  • Maximilian Seidl
    • 1
    • 2
  • Annette Schmitt-Graeff
    • 2
  • Joachim Böhm
    • 3
  • Klaudia Schrenk
    • 1
    • 2
  • Claudia Wehr
    • 1
  • Sigune Goldacker
    • 1
  • Ruth Dräger
    • 1
  • Barbara C. Gärtner
    • 4
  • Paul Fisch
    • 2
  • Martin Werner
    • 2
  • Klaus Warnatz
    • 1
    Email author
  1. 1.Center for Chronic ImmunodeficiencyUniversity Medical Center Freiburg and University of FreiburgFreiburgGermany
  2. 2.Institute of PathologyUniversity Medical Center FreiburgFreiburgGermany
  3. 3.Institute of PathologyUniversity Hospital AachenAachenGermany
  4. 4.Institute of Medical Microbiology and HygieneSaarland UniversityHomburgGermany

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