Olga Kalinina, MD, PhD
Assistant Professor
Department of Medicine
Microbiology & Immunology
- B cell repertoire in health and disease.
- Kalinina O, Louzoun Y, Wang Y, Utset T, Weigert M., Origins and specificity of auto-antibodies in Sm+ SLE patients., J Autoimmun. 2018 Jun;90:94-104.
- Kalinina O, Wang Y, Sia K, Radic M, Cazenave PA, Weigert M., Light chain editors of anti-DNA receptors in human B cells, J Exp Med. 2014 Feb 10;211(2):357-64
- Kalinina O, Doyle-Cooper CM, Miksanek J, Meng W, Prak EL, Weigert MG, Alternative mechanisms of receptor editing in autoreactive B cells. Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7125-30.
- Perera J, Zheng Z, Li S, Gudjonson H, Kalinina O, Benichou JI, Block KE, Louzoun Y, Yin D, Chong AS, Dinner AR, Weigert M, Huang H., Self-Antigen-Driven Thymic B Cell Class Switching Promotes T Cell Central Tolerance. Cell Rep. (2016) 17:387-398
- Radic M, Weigert MG, Khan SN, Han J, Kalinina O, Luning Prak ET., Antibodies that bind complex glycosaminoglycans accumulate in the Golgi, Proc Natl Acad Sci U S A
Research Interests:
Education
MD, PhD, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry (IBCh)
Moscow, Russia
Research Interests
Our lab is broadly interested in understanding how the human B cell repertoire is shaped in health and disease. The B cell repertoire arises through genetic mechanisms that generate extraordinary diversity (~10¹⁵ unique receptors), followed by selection processes that narrow it to the functional repertoire observed in humans (~10⁷). Despite this diversity, healthy individuals share remarkably similar repertoires, pointing to conserved mechanisms that balance effective pathogen defense with the prevention of autoimmunity.
A central focus of our work is to define the cellular, molecular, and environmental factors that govern these selection processes. In particular, we study how tolerance checkpoints eliminate autoreactive B cells and how these checkpoints fail in autoimmune diseases such as systemic lupus erythematosus (SLE).
We are interested in exploring the role of host–microbiota interactions in the establishment of B cell tolerance. Increasing evidence suggests that gut-associated lymphoid tissue (GALT) plays a critical role in B cell selection and diversification in humans, similar to GALT-dependent species such as chickens, rabbits, sheep, and cattle. In these species, B cells undergo antigen-independent diversification in the gut, shaped by commensal microbes. We hypothesize that a GALT-based tolerance checkpoint also exists in humans and contributes to selecting or editing B cells to promote immune tolerance. Our aim is to characterize the molecular and cellular mechanisms that enforce tolerance at this novel checkpoint, using human tissues (e.g., tonsils, appendix) and drawing parallels from animal models.
Unlike most repertoire studies that emphasize heavy-chain usage, our lab takes a distinctive approach by focusing on light-chain usage in addition to heavy chains. This perspective provides new insights into the mechanisms of human disease and has the potential to inform novel strategies for treating autoimmunity, B cell malignancies, and immunodeficiencies, as well as for designing more effective vaccines. As one example of this approach, we have developed a novel antibody that identifies a subset of light-chain–defined B cells, 80% of which produce self-reactive antibodies in SLE patients. This tool allows us to directly characterize autoreactive B cells in both patients and healthy individuals, investigate their role as biomarkers of lupus flares, and evaluate their potential as therapeutic targets.
Publications/Research Listings
Selected publications: