Centrum für Chronische Immundefizienz - CCI

Our group focuses on the development of human B cells and primary immune defects affecting B lymphocytes. Together with Klaus Warnatz and Uli Salzer we found that homozygous deletion of the BAFF-receptor gene may cause common variable immunodeficiency.

CV

Research Areas

B lymphocyte development and primary immunodeficiencies

We study the development and the immune responses of human B lymphocytes. Primary immunodeficiencies represent an unlimited pool of mutations affecting the development of B cells, the formation of memory B cells and plasma cells and the production of antibodies. Analyzing the pathomechanisms leading to primary immunodeficiencies we are trying to understand the role and function of genes regulating human B cell development and homeostasis.

Projects:

• In vitro and in vivo models of human B cell development
• BAFF-receptor signaling,B cell survival and immune responses
• Inherited defects affecting humoral immune response

Supported by:

• DFG TRR130 
• Project 06
• Novartis

Publications

PubMed

Rakhmanov M, Sic H, Kienzler AK, Fischer B, Rizzi M, Seidl M, Melkaoui K, Unger S, Moehle L, Schmit NE, Deshmukh SD, Ayata CK, Schuh W, Zhang Z, Cosset FL, Verhoeyen E, Peter HH, Voll RE, Salzer U, Eibel H, Warnatz K. High levels of SOX5 decrease proliferative capacity of human B cells, but permit plasmablast differentiation. PLoS One. 2014 Jun 19;9(6):e100328. doi: 10.1371/journal.pone.0100328. eCollection 2014.

Salzer E, Kansu A, Sic H, Májek P, Ikincioğullari A, Dogu FE, Prengemann NK, Santos-Valente E, Pickl WF, Bilic I, Ban SA, Kuloğlu Z, Demir AM, Ensari A, Colinge J, Rizzi M, Eibel H, Boztug K. Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency. J Allergy Clin Immunol. 2014 Jun;133(6):1651-9.e12. doi: 10.1016/j.jaci.2014.02.034. Epub 2014 Apr 17.

Sic, H., H. Kraus, J. Madl, K.A. Flittner, A.L. von Münchow, K. Pieper, M. Rizzi, A.K. Kienzler, C.K. Ayata, S. Rauer, B. Kleuser, U. Salzer, M. Burger, K. Zirlik, V. Lougaris, A. Plebani, W. Römer, C. Loeffler, S. Scaramuzza, A. Villa, E. Noguchi, B. Grimbacher, and H. Eibel, S1P-receptors control B cell migration through signaling components associated with primary immunodeficiencies, chronic lymphocytic leukemia and multiple sclerosis. J Allergy Clin Immunol., 2014. Accepted for publication

Kraus, H., S. Kaiser, K. Aumann, P. Bönelt, U. Salzer, D. Vestweber, M. Erlacher, M. Kunze, M. Burger, M. Pieper, H. Sic, H. Rolink, H. Eibel, and M. Rizzi, A feeder free differentiation system identifies autonomously proliferating B cell precursors in human bone marrow. J. Immunology. J Immunol, 2014. in press.

Pieper, K., M. Rizzi, M. Speletas, C.R. Smulski, H. Sic, H. Kraus, U. Salzer, G.F. Fiala, W.W. Schamel, V. Lougaris, A. Plebani, L. Hammarstrom, M. Recher, A.E. Germenis, B. Grimbacher, K. Warnatz, A.G. Rolink, P. Schneider, L.D. Notarangelo, and H. Eibel, A common SNP impairs B cell activating factor receptor's multimerization, contributing to common variable immunodeficiency. J Allergy Clin Immunol, 2013. DOI 10.1016/j.jaci.2013.11.021

Kienzler, A.K., M. Rizzi, M. Reith, S.L. Nutt, and H. Eibel, Inhibition of human B-cell development into plasmablasts by histone deacetylase inhibitor valproic acid. J Allergy Clin Immunol, 2013. 131(6): p. 1695-9.

Kreuzaler, M., M. Rauch, U. Salzer, J. Birmelin, M. Rizzi, B. Grimbacher, A. Plebani, V. Lougaris, I. Quinti, V. Thon, J. Litzman, M. Schlesier, K. Warnatz, J. Thiel, A.G. Rolink, and H. Eibel, Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. J Immunol, 2012. 188(1): p. 497-503.

Rizzi, M., R. Knoth, C.S. Hampe, P. Lorenz, M.L. Gougeon, B. Lemercier, N. Venhoff, F. Ferrera, U. Salzer, H.J. Thiesen, H.H. Peter, U.A. Walker, and H. Eibel, Long-lived plasma cells and memory B cells produce pathogenic anti-GAD65 autoantibodies in Stiff Person Syndrome. PLoS One, 2010. 5(5): p. e10838.

Eibel, H., U. Salzer, and K. Warnatz, Common variable immunodeficiency at the end of a prospering decade: towards novel gene defects and beyond. Curr Opin Allergy Clin Immunol, 2010. 10(6): p. 526-33.

Warnatz, K., U. Salzer, M. Rizzi, B. Fischer, S. Gutenberger, J. Bohm, A.K. Kienzler, Q. Pan-Hammarstrom, L. Hammarstrom, M. Rakhmanov, M. Schlesier, B. Grimbacher, H.H. Peter, and H. Eibel, B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc Natl Acad Sci U S A, 2009. 106(33): p. 13945-50. T

aubenheim, N., M. von Hornung, A. Durandy, K. Warnatz, L. Corcoran, H.H. Peter, and H. Eibel, Defined blocks in terminal plasma cell differentiation of common variable immunodeficiency patients. J Immunol, 2005. 175(8): p. 5498-503.

Team