Jan Erikson, Ph.D.

Professor
Immunology Program
215-898-3823, Office
jan@wistar.org

Introduction

To better understand autoimmune disorders, as well as responses to pathogens and vaccines, the Erikson lab investigates the interplay among different types of immune cells that result in immune system activation or suppression.  Specifically, her lab has been studying the signals that guide immune cells down distinct developmental paths that result in short-term immunity or long-lasting responses and memory formation.  These studies are highly relevant to autoimmune disease and vaccine development.

Research Summary

The Erikson laboratory is dedicated to the examination of immune cell activation and regulation.  As a hallmark of autoimmune disease is the inappropriate activation of self-reactive lymphocytes, one research objective has been to define the cellular and molecular interactions influencing self-reactive lymphocytes in healthy versus autoimmune settings. The focus has been on autoantibody producing B cells, on the role that T cells play in modifying B cell stimulation and differentiation, and on dendritic cells that are key initiators and modifiers of immune responses. To dissect the role that these cell types play in lymphocyte activation as well as tolerance to "self," in vivo mouse models have been developed that facilitate tracking the phenotypic and migratory status of self-reactive cells.
 
Recent studies have investigated the activation potential of autoreactive B cells from healthy versus autoimmune prone mice to a variety of T cell dependent as well as independent stimuli. In collaboration with Dr. Caton's laboratory at Wistar, the Erikson lab has documented that T cell help not only drives autoreactive B cell maturation and entry into the B cell follicle, but also leads to autoantibody secretion, one of the consistent features of autoimmunity.  Defining the processes that release self-reactive B cells from their tolerant state is critical to the understanding and eventual treatment of autoimmune disease. 

Interestingly, if T regulatory cells are provided in vivo along with T helper cells, early B cell activation ensues but autoantibody production is suppressed. Thus, the generation of T regulatory cells can be one strategy to maintain B cell tolerance in the face of T cell activation. Such a scenario may be occurring in young autoimmune mice where extensive T cell activation has been documented but is actively being controlled.

In a related line of investigation, inspired by the pioneering work of fellow Wistar scientist Dr. Gerhard, Dr. Erikson is beginning studies on the immune response to influenza virus with the aim of developing a vaccine to a conserved component of the virus. Dr. Erikson’s lab will use murine models to determine the optimal conditions for inducing antibody-mediated protection to influenza challenge using synthetic multiple antigenic peptides as immunogens in conjunction with distinct adjuvants.  The extent and mechanism of protection will be investigated with the expectation that these studies will inform future vaccine design strategies.

Selected Publications

Hondowicz, B.D., Alexander, S.T., Quinn III, W.J., Pagán, A.J., Metzgar, M.H., Cancro, M.P., and Erikson, J. 2007. The Role of BLyS/BLyS Receptors in Anti-Chromatin B Cell Regulation. Int Immunol. 19:465-475.

Fields, M.L., Metzgar, M.H., Hondowicz, B.D., Kang, S.-A., Alexander, S.T., Hazard, K.D., Hsu, A.C., Du, Y.-Z., Prak, E.L., Monestier, M. and Erikson, J. 2006. Exogenous and endogenous TLR ligands activate anti-chromatin ,and polyreactive B cells. J Immunol. 176:6491-6502.

Fields, M.L., Hondowicz, B.D., Metzgar, M.H., Nish, S.A., Wharton, G.N., Picca, C.C., Caton, A.J., and Erikson, J. 2005. CD4+CD25+ regulatory T cells inhibit the maturation but not the initiation of an autoantibody response. J. Immunol. 175:4255-4264.

Fields, M.L., Nish, S.A., Hondowicz, B.D., Metzgar, M.H., Wharton, G. N., Caton, A. J., and Erikson, J. 2005. The influence of effector T cells and FasL on lupus-associated B cells. J. Immunol. 175:104-111.

Srivastava, B., Quinn, W.J. 3rd, Hazard, K., Erikson, J., and Allman, D. 2005. Characterization of marginal zone B cell precursors. J Experimental Med. 202:1225-1234.

Paul, E., Lutz, J., Erikson, J., and Carroll, M.C. 2004. Germinal center checkpoints in B cell tolerance in 3H9 transgenic mice. Int. Immunol. 16: 377-384.
Busser, B.W., Adair, B.S., Erikson, J., and Laufer, T.M. 2003. Activation of diverse repertoires of autoreactive T cells enhances the loss of anti-dsDNA B cell tolerance. J. Clin. Invest. 112:1361-1371.

Fields, M.L., and Erikson, J. 2003. The regulation of lupus-associated autoantibodies: immunoglobulin transgenic models. Curr. Opinion Immunol. 15: 709-717.

Fields, M.L., Seo, S., Nish, S.A., Tsai, J.H., Caton, A.J., and Erikson, J. 2003. The regulation and activation potential of autoreactive B cells. Immunol. Res. 26:219-234.

Seo S.J., Mandik-Nayak, L., and Erikson J. 2002. B Cell Anergy and Systemic Lupus Erythematosus. In: Current Directions in Autoimmunity, (Nemazee, D., ed.) Basel, Karger, Vol. 6, pp. 1-20.

Seo, S., Fields, M.L., Buckler, J.L., Reed, A.J., Mandik-Nayak, L., Nish, S.A., Noelle, R.J., Turka, L.A., Finkelman, F.D., Caton, A., and Erikson, J. 2002. The impact of T helper and T regulatory cells on the regulation of anti-double-stranded DNA B cells. Immunity 16: 535-546.