|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
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
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