The ability to develop “immunological memory” to infectious diseases is critical for health and survival. Our laboratory studies how this long-term immunity is established and maintained in order to better understand natural immunity, improve vaccine design and develop more effective therapies for autoimmune disease.
Extensive Research Description
cells that differentiate into antigen presenting and antibody-producing cells are
important in natural and vaccine-mediated protection and are targets of B
cell-directed therapies for malignancy and autoimmune disease. Thus, there is
great interest in elucidating their unique biological properties in order to
understand how they form, function and modulate recall responses. However,
progress in elucidating these properties has been limited, particularly in
mice, by the lack of adequate markers to distinguish memory cells. Our group
has had a long-standing interest in this area and has made a number of contributions.
Using mouse systems developed in our laboratory that overcome significant barriers to the study of B cell memory, we compared gene expression between memory B cells and their naïve precursors using Affymetrix microarrays. We confirmed the differential expression of several conceptually important families at the mRNA and protein level. These initial findings were the foundation of several research projects. Some key findings and areas of ongoing research include:
1. Memory B cells are wired to signal differently than their naïve precursors.
2. There are subsets of murine memory B cells that form a spectrum from more naïve-like to more-memory-like.
3. Specific pathways regulate self-renewal and differentiation to antibody forming cells.
4. Specific pathways regulate the quality of the T-dependant B cell immune response.
- Sadanand, SS and Tomayko, MM. B Cell Biology, in Clinical and Basic Immunodermatology, Eds. Kaplan DH, Gaspari, AA, Stingl, G. In press.
- Zuccarino-Catania, GV, Sadanand, S, Weisel, FJ, Tomayko, MM, Meng, H, Kleinstein SH, Good-Jacobson, KL, Shlomchik, MH. 2014. CD80 and PD-L2 define functionally distinct memory B cell subsets that are independent of antibody isotype. Nature Immunology. 15:631-7.
- Conter, LJ, Song E, Shlomchik, MJ and Tomayko, MM. 2014. CD73 expression is dynamically regulated in the germinal center and bone marrow plasma cells are diminished in its absence. PLOS One 9(3):e92009.
- Duke JL, Liu M, Yaari G, Khalil AM, Tomayko MM, Shlomchik MJ, Schatz DG, Kleinstein SH. 2013. Multiple transcription factor binding sites predict AID targeting in non-Ig genes. J. Immunology.190(8):3878-88.
- Tomayko MM, Steinel NC, Anderson SM, Shlomchik MJ. 2010. Cutting edge: Hierarchy of maturity of murine memory B cell subsets. J. Immunology. 185:7146-50.
- Good-Jacobson, K.L., Szumilas, C.G., Chen, L, Sharpe, H.H., Tomayko, M.M., Shlomchik, M.J. 2010. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nature Immunology, 535-542.
- Scholz, J. L., J. E. Crowley, M. M. Tomayko, N. Steinel, P. J. O'Neill, W. J. Quinn, 3rd, R. Goenka, J. P. Miller, Y. H. Cho, V. Long, C. Ward, T. S. Migone, M. J. Shlomchik, and M. P. Cancro. 2008. BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact. Proc Natl Acad Sci U S A 105:15517-15522.
- Tomayko, M. M., S. M. Anderson, C. E. Brayton, S. Sadanand, N. C. Steinel, T. W. Behrens, and M. J. Shlomchik. 2008. Systematic comparison of gene expression between murine memory and naive B cells demonstrates that memory B cells have unique signaling capabilities. J Immunol 181:27-38.
- Anderson, S. M., M. M. Tomayko, A. Ahuja, A. M. Haberman, and M. J. Shlomchik. 2007. New markers for murine memory B cells that define mutated and unmutated subsets. J Exp Med 204:2103-2114.
- Anderson, S. M., M. M. Tomayko, and M. J. Shlomchik. 2006. Intrinsic properties of human and murine memory B cells. Immunol Rev 211:280-294.