Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors

• Published in: The Journal of immunology (1950) 2012-01, Vol.188 (1), p.497-503
• Main Authors: Kreuzaler, Matthias, Rauch, Melanie, Salzer, Ulrich, Birmelin, Jennifer, Rizzi, Marta, Grimbacher, Bodo, Plebani, Alessandro, Lougaris, Vassilios, Quinti, Isabella, Thon, Vojtech, Litzman, Jiri, Schlesier, Michael, Warnatz, Klaus, Thiel, Jens, Rolink, Antonius G, Eibel, Hermann
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Animals; Antibodies, Monoclonal, Murine-Derived - pharmacology; B-Cell Activating Factor - blood; B-Cell Activating Factor - immunology; B-Cell Activation Factor Receptor - immunology; B-Cell Activation Factor Receptor - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Child; Child, Preschool; Humans; Immunologic Deficiency Syndromes - blood; Immunologic Deficiency Syndromes - immunology; Infant; Leukemia, Lymphocytic, Chronic, B-Cell - blood; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Lymphocyte Count; Mice; Mice, Inbred BALB C; Mice, Transgenic; Middle Aged; Rats; Rats, Inbred Lew
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1102321

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.