Ronald Jemmerson, PhD

Professor Emeritus, Department of Microbiology and Immunology

Ronald Jemmerson

Contact Info

PhD, Northwestern University, 1978


Research Summary/Interests

Antigen-Antibody Interactions; Apoptosis

My laboratory contributed to the seminal study showing that cytochrome c (Cyt c) translocates from mitochondria to the cytoplasm during apoptosis and plays a key role in the activation of programmed cell death (Cell 86:147-157, 1996). One monoclonal antibody specific for the native protein was used to remove Cyt c, thus showing that this protein and not a contaminant was responsible for the pro-apoptotic activity and another monoclonal antibody specific for the carboxyl terminal dodecapeptide was used to show Cyt c translocation to the cytoplasm by Western blotting. Later we found that Cyt c is released from apoptotic cells as an intact protein (Cell Death Differ. 9:538-548, 2002). Consequently, Cyt c has been explored as a potential clinical biomarker for aberrant apoptosis in vivo.

While developing an immunoassay to detect Cyt c in serum we discovered that leucine-rich alpha-2-glycoprotein-1 (LRG1) binds Cyt c and inhibits its detection in an antibody-based assay (Apoptosis 11:1121-1129, 2006). LRG1 has been implicated as a biomarker for a variety of cancers and microbial infections. However, its function was unknown. We have shown that LRG1 binds Cyt c in a manner similar to that of the protein Apaf-1 that initiates the intrinsic pathway of apoptosis. In vitro serum LRG1 acts as a survival protein extending the half -life of lymphocytes (Apoptosis 15:139-152, 2010). Recently, we demonstrated that, in MCF-7 breast cancer cells, cytoplasmic LRG1 competes with Apaf-1 for binding Cyt c in situ and, thus, inhibits the onset of apoptosis. We developed an enzyme-linked immunosorbent assay for LRG1 that may be useful clinically (J. Immunol. Methods 336:22-29, 2008).

Our apoptosis-related research evolved from studies of antibody recognition employing Cyt c as the model antigen. We made a number of observations that give insight into the antibody response with implications for vaccine development. We uncovered an artifact in immunoassays that misled researchers into believing that peptides could be broadly used as vaccines (PNAS 84:9180-9184, 1987). Even when a peptide can bind antibodies elicited against a native protein antigen this does not necessarily indicate that the peptide can activate B cells producing those antibodies as a certain affinity threshold must be met (Mol. Immunol. 26:301-307, 1989). We also showed that approximately 10% of memory B cells can be activated in an environment of T cell help in the absence of the cognate B cell antigen (Eur. J. Immunol. 21:951-958). This may explain, at least in part, the longevity of B cell memory after antigen has been depleted in vivo. We found that affinity maturation in the antibody response to a protein antigen follows the paradigm established for responses to smaller chemical compounds. Thus, an affinity increase of several hundred fold can result from DNA mutations at only a few key nucleotide positions in antibody genes (J. Immunol. 157:5329-5338, 1996). Much more about this phenomenon is explained in a follow-up review (Recent Res. Dev. Immunol. 4:13-25, 2002).

A surprising observation was a higher frequency of B lymphocytes in mice specific for mouse Cyt c than for foreign Cyts c (Eur. J. Immunol. 25:784-791, 1995). The autoreactive B cells generally expressed the same antibody heavy and light chain genes but were quite variable in CDR3 of the heavy chain. We speculate that mouse Cyt c may serve as a ligand for B cell positive selection. Supporting this idea, the antibody response to the closely related pigeon Cyt c actually initiates as a response more specific for mouse Cyt c utilizing those same variable region genes and eventually becomes more specific for pigeon Cyt c (PNAS 92:12379-12383, 1995).


  • Jemmerson, R., Staskus, K., Higgins, L., Conklin, K., and Kelekar, A. 2021. Intracellular leucine-rich alpha-2-glycoprotein-1 competes with Apaf-1 for binding cytochrome c in protecting MCF-7 breast cancer cells from apoptosis. Apoptosis 26:71-82.
    Hannibal, L., Tomasina, F., Capdevila, D.A., Demicheli, V., Tortora, V., Alvarez-Paggi, D., Jemmerson, R., Murgida, D.H., and Radi, R. 2016. Alternative conformations of cytochrome c: Structure, function, and detection. Biochemistry 55:407-428.
  • Lowman, X.H., McDonnell, M.A., Kosloske, A., Odumade, O.A., Jenness, C.B.,Jemmerson, R., and Kelekar, A. 2010. The proapoptotic Function of Noxa in human leukemia cells is regulated by the kinase Cdk5 and by glucose.Molecular Cell. 40:823-833.
  • Codina, R., Vanasse, A. Kelekar, A., Vezys, V., andJemmerson, R.2010. Cytochromec-induced lymphotyte death from the outside in: Inhibition by serum leucine-rich alpha-2-glycoprotein-1. Apoptosis 15: 139-152.
  • Cummings, C., Walder, J., Treeful, A., andJemmerson, R.2006. Serum leucine-rich alpha-2-glycoprotein-1 binds cytochromecand inhibits antibody detection of this apoptotic marker in enzyme-linked immunosorbent assay.Apoptosis 11:1121-1129.
  • Jemmerson, R., Dubinsky, J. M., and Brustovetsky, N. 2005. Cytochrome c release from CNS mitochondria and potential for clinical intervention in apoptosis-mediated CNS diseases. Antioxid. Redox Signal. 7:1158-1172.
  • Brustovetsky, N., Dubinsky, J. M., Antonsson, B., andJemmerson, R.2003. Two pathways for tBID-induced cytochromecrelease from rat brain mitochondria: BAK- versus BAX-dependence. J. Neurochem. 84:196-207.
  • Jemmerson, R., LaPlante, B., and Treeful, A. 2002. Release of intact, monomeric cytochromec from apoptotic and necrotic cells.Cell Death and Differentiation 9:538-548.
  • Jemmerson, R.2002.The molecular basis for affinity maturation in the antibody response to a protein antigen, cytochromec.Recent. Res. Devel. Immunology 4:13-25.
  • Liu, X., Kim, C.N.,Jemmerson, R., Wang, X. 1996. Induction of apoptotic program in cell-free extracts: Requirement for dATP and Cytochromec.Cell 86:147-157.
  • Mueller, C.M.,Jemmerson, R.1996. Maturation of the antibody response to the major epitope on the self antigen mouse cytochromec.J. Immunol 157:5329-5338.
  • Minnerath, J.M., Mueller, C.M., Buron, S., and Jemmerson, R. 1995. B lymphocyte recognition of cytochrome c: Higher frequency of cells specific for self vs. foreign antigen early in the response and V gene usage in response to self antigen. Eur. J. Immunol. 25:784-791.
  • Minerath, J.M., Wakem, L.P., Comfort, L.L., Sherman, F., and Jemmerson, R. (1995) The BALB/c mouse B cell response to pigeon cytochrome c initiates as a heteroclitic response specific for the self antigen mouse cytochrome c. Proc. Natl. Acad. Sci. U.S.A. 92:12379-12383.
  • Jemmerson R. and Blankenfeld, R. 1989. Affinity consideration in the design of synthetic vaccines intended to elicit antibodies. Mol. Immunol. 26:301-307.
  • Johnson, J.G. and Jemmerson, R. 1991. Relative frequencies of secondary B cells activated by cognate versus other mechanisms. Eur. J. Immunol. 21:951-958.
  • Jemmerson, R.1987. Antigenicity and native structure of globular proteins: Low frequency of peptide reactive antibodies.Proc. Natl. Acad. Sci. USA. 84:9180-9184.
  • Jemmerson, R.and Paterson, Y. 1986. Mapping epitopes on protein antigens by the proteolysis of antigen-antibody complexes.Science 232:1001-1004.