Soluble BAFF Levels Inversely Correlate with Peripheral B Cell Numbers and the Expression of BAFF Receptors

KREUZALER, Matthias, Melanie RAUCH, Ulrich SALZER, Jennifer BIRMELIN, Marta RIZZI, Bodo GRIMBACHER, Alessandro PLEBANI, Vassilios LOUGARIS, Isabella QUINTI, Vojtěch THON, Jiří LITZMAN, Michael SCHLESIER, Klaus WARNATZ, Jens THIEL, Antonius G. ROLINK and Hermann EIBEL. Soluble BAFF Levels Inversely Correlate with Peripheral B Cell Numbers and the Expression of BAFF Receptors. The Journal of Immunology. 2012, vol. 188, No 1, p. 497-503. ISSN 0022-1767. Available from: https://dx.doi.org/10.4049/jimmunol.1102321.

Basic information

• Original name: Soluble BAFF Levels Inversely Correlate with Peripheral B Cell Numbers and the Expression of BAFF Receptors
• Authors: KREUZALER, Matthias (756 Switzerland, guarantor), Melanie RAUCH (756 Switzerland), Ulrich SALZER (276 Germany), Jennifer BIRMELIN (826 United Kingdom of Great Britain and Northern Ireland), Marta RIZZI (276 Germany), Bodo GRIMBACHER (826 United Kingdom of Great Britain and Northern Ireland), Alessandro PLEBANI (380 Italy), Vassilios LOUGARIS (380 Italy), Isabella QUINTI (380 Italy), Vojtěch THON (203 Czech Republic, belonging to the institution), Jiří LITZMAN (203 Czech Republic, belonging to the institution), Michael SCHLESIER (276 Germany), Klaus WARNATZ (276 Germany), Jens THIEL (276 Germany), Antonius G. ROLINK (756 Switzerland) and Hermann EIBEL (276 Germany).
• Edition: The Journal of Immunology, 2012, 0022-1767.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30300 3.3 Health sciences
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 5.520
• RIV identification code: RIV/00216224:14110/12:00059246
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.4049/jimmunol.1102321
• UT WoS: 000298628400057
• Keywords in English: chronic lymphocytic leukemia; Creactive protein; common variable immunodeficiency; primary antibody deficiency; systemic lupus erythematosus
• Tags: International impact, Reviewed

Abstract

The TNF family member protein BAFF/BLyS is essential for B cell survival and plays an important role in regulating class switch recombination as well as in the selection of autoreactive B cells. In humans, increased concentrations of soluble BAFF are found in different pathological conditions, which may be as diverse as autoimmune diseases, B cell malignancies, and primary Ab deficiencies (PAD). Because the mechanisms that regulate BAFF levels are not well understood, we newly developed a set of mAbs against human BAFF to study the parameters that determine the concentrations of soluble BAFF in circulation. Patients with PAD, including severe functional B cell defects such as BTK, BAFF-R, or TACI deficiency, were found to have higher BAFF levels than asplenic individuals, patients after anti-CD20 B cell depletion, chronic lymphocytic leukemia patients, or healthy donors. In a comparable manner, mice constitutively expressing human BAFF were found to have higher concentrations of BAFF in the absence than in the presence of B cells. Therefore, our data strongly suggest that BAFF steady-state concentrations mainly depend on the number of B cells as well as on the expression of BAFF-binding receptors. Because most patients with PAD have high levels of circulating BAFF, the increase in BAFF concentrations cannot compensate defects in B cell development and function.

Links

• 7E08062, research and development project: Name: Pathophysiology and Natural Course of Primary Antibody Deficiency (PAD) Syndromes

Investor: Ministry of Education, Youth and Sports of the CR, Pathophysiology and Natural Course of Primary Antibody Deficiency (PAD) Syndromes