Research Program:
Effective host immune defense depends on the coordinated response of both innate and adaptive arms of the immune system and the directed migration of leukocytes to chemoattractants is an integral component of both responses. Chemokine and lysophospholipid chemoattractants signal via their respective G-protein coupled receptors (GPCRs) expressed by hematopoietic cells. The overall focus of our laboratory investigates how lymphocytes and cells of the innate immune system regulate migration and adhesion during homeostatic and inflammatory conditions. To address these issues, we employ complementary systems that rely on molecular, cellular, and genetic approaches coupled to in vivo and in vitro analyses of leukocyte migration and adhesion.

BCR regulation of migration and adhesion in B cell development and function
Immature B cells develop in the adult bone marrow within a microenviroment that includes contact with stromal cells expressing cytokines, chemokines and adhesion molecules that promote appropriate maturation. As soon as immature B cells express a B cell antigen receptor (BCR) on the surface, it is tested for self-reactivity and immature B cells harboring a non-autoreactive antigen receptor emigrate to the periphery whereas autoreactive immature B cells are retained in the bone marrow and rendered tolerant. As a mature B lymphocyte in peripheral tissues, encounter with foreign antigen leads to an antibody response that facilitates the neutralization and clearance of the potential pathogen. BCR signaling by mature B lymphocytes differs in significant ways compared with bone marrow immature B cells. Yet, similar to immature B cells, BCR signaling by mature B cells also influences the subsequent trafficking of the activated cell through alterations in chemoattractant responsiveness and integrin adhesion. This regulation of chemoattractant migration after antigen recognition plays an important in vivo role during an immune response by directing antigen-activated B lymphocytes to microenvironments that induce appropriate antibody production. Thus, a common feature of antigen receptor signaling exhibited by both immature and mature B cells is the subsequent directed migration of the cell for appropriate further differentiation. Work in our lab uses in vivo and in vitro approaches to investigate how BCR signaling influences both chemoattractant responsiveness and integrin adhesion of marginal zone and follicular B cells to accomplish these events.

Regulation of leukocyte migration and adhesion in lung immunity
Leukocytes are resident in the lungs of healthy individuals and are necessary for orchestrating the innate and adaptive immune response towards the antigenic challenges that are inspired on a constant basis. However, inappropriate regulation of lung immunity can also lead to chronic inflammation and subsequent tissue damage and pathophysiology, hallmarks of both asthma and chronic obstructive pulmonary disease. An additional area of investigation in our lab examines how leukocytes regulate chemoattractant responsiveness and cell adhesion during inflammation in the lung and how aberrant regulation of these processes may facilitate these inflammatory lung diseases.

Key Publications:

• Brown, J., Taube, C., Takeda, K, Koya, T., Pelanda, R., Gelfand, E.W., and Torres, R.M.(2007) Arhgef1 is Required by T cells for the Development of Airway Hyperreactivity and Inflammation. American Journal of Respiratory Critical Care Medicine, 176:10-19.
• Pelanda, R. and Torres, R.M. (2006) Receptor editing for better or for worse. Current Opinion in Immunology. 18:184-190.
• Rubtsov, A., Strauch, P., DiGiacomo, A., Hu, J., Pelanda, R and Torres, R.M. (2005) Lsc Regulates Marginal Zone B cell Migration and Adherence and is Required for the IgM T-dependent Antibody Response. Immunity, 23:527-538.
• Halverson, R., Torres, R.M., and Pelanda, R. (2004) Receptor editing is the primary mechanism of B cell tolerance towards membrane antigens. Nature Immunology, 5:645-650, 2004.
• Torres, R.M. and Hafen, K. (1999) Ig-alpha has an inhibitory role in early B cell development. Immunity 11:527-536.
• Kraus, M., Saijo, K., Torres, R.M., and Rajewsky, K. (1999) Ig-alpha cytoplasmic truncation renders immature B cells more sensitive to antigen contact. Immunity 11:537-545.
• Torres, R.M. and Kühn, R. (1997). Laboratory Protocols for Conditional Gene Targeting. Oxford University Press, Oxford. 192 pages.
• Pelanda, R., Schall, S., Torres, R.M., and Rajewsky, K. (1996). A prematurely expressed Igκ transgene, but not a VκJκ gene segment targeted into the Igκ locus, can rescue B cell development in a λ 5-deficient mice. Immunity 5:229-239.
• Torres, R.M., Flaswinkel, H., Reth, M., and Rajewsky, K. (1996). Aberrant B cell development and immune response in mice with a compromised BCR complex. Science 272:1804-180

View of Recent Publications in PubMed