Timothy Manser, Ph.D.

Professor and Chair

Microbiology & Immunology

Antigen-Driven B Cell Differentiation and Autoimmunity


Office Address
471 Jefferson Alumni Hall
233 S. 10th Street, Philadelphia, PA 19107

Email Address


Interest in our laboratory centers around the mechanisms that regulate development of the memory B cell compartment. We focus on the role the B cell antigen receptor plays in this process, but are also investigating how several other receptors and cytokines influence this pathway.  The projects currently being pursued include: 1. Defining the influence of antigen receptor affinity, autoreactivity and level of expression on B cell positive and negative selection. 2. Investigation of the functional relevance of cellular subcompartments of the germinal center. 3. Elucidation of the role of FcgammaRIIB in regulation of memory B cell development. 4. Investigation of the influence of BAFF (BLyS) on the germinal center reaction and memory B cell development and maintenance.

Keywords: antibody diversity, somatic hypermutation, memory B cell, clonal selection, autoantibodies

PubMed Link For Manser T

Selected Publications

Rahman, Z.S.M., S.P. Rao, S. Kalled and T. Manser “Normal Induction but Attenuated Progression of Germinal Center Responses in BAFF and BAFF-R Signaling Deficient Mice”, (2003) J. Exp. Med., 198: 1157-1169.

Tumas-Brundage, K. and T. Manser, "The Transcriptional Promoter Regulates Hypermutation of the Antibody Heavy Chain Locus", (1997) J. Exp. Med. 185; 239-250.

Vora, K.A., J.V. Ravetch and T. Manser, "Amplified Follicular Immune Complex Deposition in Mice Lacking the Fc Receptor gamma-chain does not Alter Maturation of the B Cell Response", (1997) J. Immunol. 159: 2116-2124.

Vora, K.A., K. Tumas-Brundage and T. Manser. "A PALS-associated B Cell Focus Response is not Observed During the Development of the Anti-arsonate Germinal Center Reaction", (1998) J. Immunol. 160: 728-733.

Hande, S., E. Notidis and T. Manser. "Bcl-2 Obstructs Negative Selection of Autoreactive, Hypermutated Antibody V Regions During Memory B Cell Development". (1998) Immunity 8: 189-198.

Manser, T., Tumas-Brundage, K., Casson, L.P., Giusti, A., Notidis, E., Hande, S. and Vora, K.: The roles of antibody V region hypermutation and selection in the development of the memory B cell compartment. Immunology Rev. 162: 183-196, 1998.

Vora, K.A., K. Tumas-Brundage, V. Lentz, A. Cranston, R. Fishel and T. Manser "Severe Attenuation of the B cell Immune Response in MSH2-deficient Mice", (1999) J. Exp. Med. 189: 471-481.

Vora , K.A., K. Tumas-Brundage and T. Manser "Contrasting the in situ Behavior of a Memory B Cell Clone During Primary and Secondary Immune Responses" (1999) J. Immunol., 163: 4315-4327.

Benschop, R.J. K. Aviszus, X. Zhang, T. Manser, J.C. Cambier and L.J. Wysocki "Activation and Anergy in Bone Marrow B Cells of a Novel Immunoglobulin Transgenic Mouse that is both Hapten-specific and Autoreactive" (2001) Immunity 14: 33-43.

Vora, K. A., V.M. Lentz, R. Mettus, S.P. Rao, E.P. Reddy and T. Manser. "The T Cell Dependent B Cell Response and Germinal Center Reaction are Intact in A-myb-Deficient Mice" (2001) J. Immunol. 166: 3226-3230.

Lentz, V.M. and T. Manser "Cutting Edge: Germinal Centers can be Induced in the Absence of T Cells" (2001) J. Immunol. 167: 15-20.

Heltemes, L. and T. Manser "Level of BCR Surface Expression Influences both Positive and Negative Selection during Primary B Cell Development" (2002) J. Immunol., 169: 1283-1292.

Rao, S.P., K.A. Vora and T. Manser "Expression of the Inhibitory Fc Receptor FcgRIIb by Germinal Center Cells: Implications for the Selection of High Affinity B Cells" (2002) J. Immunol., 169: 1859-1868.

Notidis, E., L. Heltemes and T. Manser "Dominant, Heirarchical Induction of Self-tolerance During Foreign Antigen-Driven B Cell Development" (2002) Immunity 17: 317-327.

Alabyev, B. and T. Manser "Bcl-2 Rescues the Germinal Center Response but does not Alter the Hypermutation Spectrum in MSH2 Deficient Mice" (2002) J. Immunol. 169: 3819-3824.

Rahman, Z.S.M., S.P. Rao, S. Kalled and T. Manser "Normal Induction but Attenuated Progression of Germinal Center Responses in BAFF and BAFF-R Signaling Deficient Mice", (2003) J. Exp. Med., 198: 1157-1169.

Heltemes-Harris, L.M., X. Liu and T. Manser, "Progressive Surface BCR Downregulation Accompanies Efficient Development of Anti-Nuclear Antigen B Cells to Mature, Follicular Phenotype"(2004) J. Immunol., in press

Web page revised: September 17, 2014.
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