Beyond their critical role in humoral immunity, B lymphocytes are also capable of suppressing immune responses. There is strong evidence that “regulatory” B cells can suppress autoimmune disease in a variety of mouse models of human autoimmune diseases. Our work focuses on “killer” B cells, a type of regulatory B cell defined by expression of the death-inducing molecule Fas ligand (FasL). Conceptually, FasL+ B cells uniquely possess the potential for suppression that is both antigen-specific, as only T cells recognizing antigens presented by FasL+ B cells are targeted, and permanent, as FasL signaling leads to cell death in target cells. Our lab is broadly focused on identifying factors governing FasL+ B cell frequency and function, as this knowledge might aid in designing treatment strategies that increase FasL+ B cell activity or target antigen-specific T cells in patients with autoimmunity.
Klinker MW, Lundy SK; “Multiple Mechanisms of Immune Suppression by B Lymphocytes.” Molecular Medicine, 18(1):123-137, February 2012. PMID: 22033729
Klinker MW, Schiller JJ, Magnuson VL, Wang T, Basken J, Veth K, Pearce KI, Kinnunen L, Harjutsalo V, Wang X, Toumilehto J, Sarti C, Ghosh S. Single-nucleotide polymorphisms in the IL2RA gene are associated with age at diagnosis in late-onset Finnish type 1 diabetes subjects. Immunogenetics 62(2):101-107, Feb 2010. PMID20033399.
Glisic S, Klinker MW, Waukau J, Jailwala P, Jana S, Basken J, Wang T, Alemzadeh R, Hagopian W, Ghosh S. Genetic association of HLA DQB1 with CD4+CD25+(high) T-cell apoptosis in type 1 diabetes. Genes Immun. 10(4):334-340, June 2009. PMID19295543.
Klinker MW, Alzua B, Reed T, Shaw C, Fox DA, Lundy SK. “FasL+ Regulatory B Cells Are Expanded by Interleukin-5 and Induce Apoptosis in CD4+ T Cells Via Cell-Cell Contact and Secretion of FasL+ Exosomes.” American College of Rheumatology/Association of Rheumatology Health Professionals Annual Scientific Meeting, November 2011, Chicago, Illinois.
Lundy SK*, Alzua B, Reed TJ, Klinker MW. “Splenic FasL+CD5+ B lymphocytes are distinct from peritoneal B-1a cells and expand in response to interleukin-5.” Annual Meeting of the American Association of Immunologists, May 2011, San Francisco, California.
Lundy SK*, Alzua B, Reed TJ, Klinker MW. “Killer B lymphocytes: Phenotype and growth characteristics.” Keystone Symposium on B Cells, April 2011, Whistler, British Columbia, Canada.
Klinker M*, Reed TJ, Shaw C, Fox D, Holoshitz J, Lundy S. “B cell-derived lymphoblastoid cell lines secrete MHCII+FasL+ exosomes.” Autumn Immunology Conference, Nov 2010, Chicago, Illinois.
Klinker MW, Shaw CG, Reed TJ, Fobare AM, Fox DA, Holoshitz J, Lundy SK. “Citrullinated Proteins in EBV Lines with Divergent Cytokine Profiles: Implications for Maintenance and Breakage of Immune Tolerance”. Keystone Symposium on Immune Tolerance, Feb. 2010, Taos, NM.
Klinker M, Shaw C, Reed T, Fobare A, Fox D, Holoshitz J, Lundy S “Characterization of Fas ligand expression in human B cell-derived lymphoblastoid cell lines”. Autumn Immunology Conference, Nov. 2009, Chicago, IL.
Lundy SK, Klinker M, Shaw CG, Reed TJ, Wooley LE, Fox DA. “Reduced Fas ligand-expressing CD5+ B lymphocytes in severe collagen-induced arthritis.” American College of Rheumatology, ‘Within Our Reach’ Research Meeting, June 2009, San Diego, CA.
Jailwala PA, Waukau J, Glisic-Milosavljevic S, Jana S, Ehlenbach S, Klinker M, Hessner M, Schiller J, Alemzadeh R, Hagopian W, Matsuyama S, Laud P, Wang X, Ghosh S; Gene expression signatures in CD4+CD25+high T cells from Recent-onset T1D subjects reveal evidence for increased sensitivity to apoptosis, partially mediated by IL-2 deprivation; ADA 69th Scientific Sessions, June 5-9 2009, New Orleans, Louisiana.
Glisic S, Klinker M, Waukau J, Jailwala P, Jana S, Basken J, Wang T, Alemzadeh A, Ghosh S; Increase CD4+CD25+high T cell apoptosis and HLA-DQ haplotypes in Type 1 diabetes; Keystone Symposia, Mar 1-6, 2009, Keystone, Colorado.
Schiller J, Klinker M, Magnuson V, Wang T, Basken J, Luczkowski E, Koppen M, Kramer J, Harjutsalo V, Valle TT, Ghosh S. HLA-DQ determines age-at-onset in early-onset T1D while the insulin locus determines age-at-onset in late-onset T1D. 9th International Congress of the Immunology of Diabetes Society and American Diabetes Association Research Symposium, Nov 14-18, 2007, Miami Beach, Florida.
Glisic-Milosavljevic S, Klinker M, Basken J, Schiller JJ, Jailwala P, Waukau J, Ehlenbach S, Koppen M, Kramer J, Jana S, Luczkowski E, Alemzadeh R, Ghosh S. HLA association with elevated CD4+D25+high T cell apoptosis. 9th International Congress of the Immunology of Diabetes Society and American Diabetes Association Research Symposium, Nov 14-18, 2007, Miami Beach, Florida.
Jailwala P, Waukau J, Glisic-Milosavljevic S, Ehlenbach S, Jana S, Koppen M, Kramer J, Hessner M, Klinker M, Basken J, Schiller J, Luczkowski E and Ghosh S. Identification of disease-specific genes in T1D through genetics of gene expression in regulatory T cells. 9th International Congress of the Immunology of Diabetes Society and American Diabetes Association Research Symposium, Nov 14-18 2007,Miami Beach, Florida.
Jailwala P, Waukau J, Glisic-Milosavljevic S, Ehlenbach S, Koppen M, Klinker M, Hessner M, Schiller J, Alemzadeh R, Ghosh S. Identification of HLA-specific and disease-specific genes in T1D through genetics of gene expression in regulatory T cells. ADA 67th Scientific Sessions, June 22-26 2007, Chicago, Illinois.
Herman and Dorothy Miller Award for Innovative Immunology Research, 2012