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Germinal Center Reutilization By Newly Activated B Cells., Tanja A Schwickert, Boris Alabyev, Tim Manser, Michel C Nussenzweig Dec 2009

Germinal Center Reutilization By Newly Activated B Cells., Tanja A Schwickert, Boris Alabyev, Tim Manser, Michel C Nussenzweig

Department of Microbiology and Immunology Faculty Papers

Germinal centers (GCs) are specialized structures in which B lymphocytes undergo clonal expansion, class switch recombination, somatic hypermutation, and affinity maturation. Although these structures were previously thought to contain a limited number of isolated B cell clones, recent in vivo imaging studies revealed that they are in fact dynamic and appear to be open to their environment. We demonstrate that B cells can colonize heterologous GCs. Invasion of primary GCs after subsequent immunization is most efficient when T cell help is shared by the two immune responses; however, it also occurs when the immune responses are entirely unrelated. We conclude …


Lineage-Specific T-Cell Responses To Cancer Mucosa Antigen Oppose Systemic Metastases Without Mucosal Inflammatory Disease., Adam E. Snook, Peng Li, Benjamin J Stafford, Elizabeth J Faul, Lan Huang, Ruth C Birbe, Alessandro Bombonati, Stephanie Schulz, Matthias J. Schnell, Laurence C. Eisenlohr, Scott A. Waldman Apr 2009

Lineage-Specific T-Cell Responses To Cancer Mucosa Antigen Oppose Systemic Metastases Without Mucosal Inflammatory Disease., Adam E. Snook, Peng Li, Benjamin J Stafford, Elizabeth J Faul, Lan Huang, Ruth C Birbe, Alessandro Bombonati, Stephanie Schulz, Matthias J. Schnell, Laurence C. Eisenlohr, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Cancer mucosa antigens are emerging as a new category of self-antigens expressed normally in immunologically privileged mucosal compartments and universally by their derivative tumors. These antigens leverage the established immunologic partitioning of systemic and mucosal compartments, limiting tolerance opposing systemic antitumor efficacy. An unresolved issue surrounding self-antigens as immunotherapeutic targets is autoimmunity following systemic immunization. In the context of cancer mucosa antigens, immune effectors to self-antigens risk amplifying mucosal inflammatory disease promoting carcinogenesis. Here, we examined the relationship between immunotherapy for systemic colon cancer metastases targeting the intestinal cancer mucosa antigen guanylyl cyclase C (GCC) and its effect on inflammatory …