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Roberta Pelanda PhD

Professor of Immunology


 

 

 

 


Education: PhD, cellular and molecular biology, Italy
Phone: 303-398-1451 (office); 303-398-1089 (lab)
E-mail: PelandaR@NJHealth.org 
Lab Room: K814
Dr. Pelanda's National Jewish Health webpage

 

The capacity of the adaptive immune system to mount an efficacious response against all sorts of external insults depends on the development of a wide repertoire of B cell specificities encoded by immunoglobulin (Ig) heavy and light chains.  Ig genes are generated via random gene rearrangement events during the development of immature B cells and thus can encode either non-self (foreign) or self-reactive (autoreactive) specificities.  Autoreactivity leads to negative selection (tolerance) while reactivity toward foreign antigens results in the activation and proliferation of B cells.  Our lab is interested in uncovering the molecular pathways that guide the development, selection and activation of autoreactive and non-autoreactive B cells and that, thus, lead to the generation of the naïve B cell repertoire.

 

B cell tolerance: Receptor editing is a mechanism of central tolerance that, via secondary Ig gene rearrangement(s), renders autoreactive B cells non-autoreactive. Our studies have determined that high-avidity autoreactive immature B cells undergo tolerance via receptor editing and not clonal deletion. We have shown that clonal deletion is not a significant tolerance mechanism unless receptor editing is inhibited. We are currently investigating the molecular events that lead autoreactive B cells to undergo tolerance.

 

Positive selection: Non-autoreactive immature B cells undergo “positive” selection: this is a process that results in the migration of newly generated B cells out of the bone marrow, in the differentiation of immature B cells into mature B cells, and the entry of new B cells into the peripheral B cell pool.  Positive selection appears to be mediated by ligand-independent tonic B cell receptor (BCR) signaling. Our lab is interested in understanding the nature of this “positive” signal and in which way it differentiates from antigen-mediated signal. We are characterizing the molecular mediators of the tonic BCR signaling cascade in immature B cells to identify those that lead to the generation of mature B cells.

 

Autoimmunity: Perturbation of immature B cell selection can result in the development of mature autoreactive B cells that, if activated, can then lead to autoimmune diseases.  We have found that autoantibody-producing immature B cells can be positively selected when they co-express non-autoreactive antibodies.  Dual antibody-expressing B cells are a small B cell sub-population in normal mice and humans, but our recent findings indicate that their numbers positively correlate with autoimmunity in mice. Studies in the lab focus at understanding the molecular pathways that lead to the development of dual antibody-expressing B cells and their contribution to autoimmunity in mice and humans.  In additional studies, we have found that mouse gamma-herpes virus infections prevent the development of autoimmunity in disease-prone mice. We are interested in finding out how these viruses prevent these chronic diseases.

 

Human B cells: We use hematopoietic humanized mice to determine how human B cells develop and undergo selection.  Hematopoietic humanized mice are generated by transplanting human hematopoietic stem cells from umbilical cord blood into immunodeficient mice. With these mice we are currently investigating how human autoreactive B cells undergo tolerance and the factors that drive the generation of mature human B cells.


 

 

  • Pelanda, R., S. Schaal, R.M. Torres, and K. Rajewsky. 1996. A prematurely expressed Ig(kappa) transgene, but not V(kappa)J(kappa) gene segment targeted into the Ig(kappa) locus, can rescue B cell development in lambda5-deficient mice. Immunity 5:3:229-39. PMID: 8808678.
  • Pelanda, R., S. Schwers, E. Sonoda, R.M. Torres, D. Nemazee, and K. Rajewsky. 1997. Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification. Immunity 7:6:765-75. PMID: 9430222.

  • Pelanda R., U. Braun, E. Hobeika, M.C. Nussenzweig, and M. Reth. 2002. B Cell Progenitors Are Arrested in Maturation but Have Intact VDJ Recombination in the Absence of Ig-alpha and Ig-beta. J Immunol, 169:865-872. PMID: 12097390. Faculty of 1000 Biology: http://f1000.com/1009168.  

  • Halverson, R,. R.M. Torres, and R. Pelanda, 2004. Receptor editing is the primary mechanism of B cell tolerance toward membrane antigens. Nature Immunology, 5(6):645-50. PMID: 15156139.

  • Liu S., Velez M.G., Humann J., Rowland S., Conrad F.J., Halverson R., Torres R.M., and Pelanda R., 2005. Receptor editing can lead to allelic inclusion and development of B cells that retain antibodies reacting with high avidity autoantigens.  J Immunol, 175:5067-5076. PMID: 16210610.

  • Velez M.G., Kane M., Liu S., Gauld S.B., Cambier J.C., Torres R.M., and Pelanda R., 2007. Ig allotypic inclusion does not prevent B cell development or response, J Immunol, 179:1049-1057. PMID: 17617597.

  • Hobeika E., Thiemann S., Storch B., Jumaa H., Nielsen P.J., Pelanda R., and Reth M., 2006. Testing gene function early in the B cell lineage in mb1-cre mice.  Proc Natl Acad Sci U S A. 103, no. 37:13789-13794. PMID: 16940357.

  • Rowland S.L., DePersis C.L., Torres R.M., and Pelanda R., 2010. Ras activation of Erk restores impaired tonic BCR signaling and rescues immature B cell differentiation. JEM, 207(3):607-21. PMID: 20176802.

  • Rowland S.L., Leahy K.F., Halverson R., Torres R.M., and Pelanda R., 2010. BAFF-R signaling aids the differentiation of immature B cells into transitional B cells following tonic BCR signaling. JI, 185(8):4570-81. PMID: 20861359.

  • Lang J., N. Weiss, R. Torres, and R. Pelanda, 2011. Generation of hematopoietic humanized mice in the newborn BALB/c Rag2-/-Il2rg-/- mouse model: a multivariable optimization approach. Clinical Immunology. 140(1):102-16. PMID: 21536497.

  • Teodorovic S.L., C. Riccardi, R.M. Torres, and R. Pelanda, 2012.  Murine B cell development and antibody responses to model antigens are not impaired in the absence of the TNF receptor GITR. PLoS One 2012;7(2):e31632. PMID: 22328941. PMCID:PMC3273462.

  • Larson J.D., J.M. Thurman, A.V. Rubtsov, D. Claypool, P. Marrack, L.F. van Dyk, R.M. Torres, and R. Pelanda, 2012.  Murine gammaherpesvirus 68 infection protects lupus-prone mice from the development of autoimmunity. Proc Natl Acad Sci U S A, 109(18):E1093-100. PMID: 22474381. PMCID:PMC3345002. Faculty of 1000 Biology: http://f1000.com/717952727. Highlighted in ScienceNews and ScienceDaily.

  • Fournier E.M., M.G. Velez, K. Leahy, C.L. Swanson, A.V. Rubtsov, R.M. Torres, and R. Pelanda, 2012. Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice. J Exp Med, 209(10):1797-812.PMCID:22927551. Faculty of 1000 Biology: http://f1000.com/717954496.

  • Pelanda, R., and R.M. Torres, 2012. Central B-cell tolerance: where selection begins. Cold Spring Harb Perspect Biol, 2012 Apr 1, 4(4):a007146. doi: 10.1101/cshperspect.a007146. PMID: 22378602.

  • Lang J., M. Kelly, Brian M. Freed, Martin D. McCarter, Ross M. Kedl, R. Torres, and R. Pelanda, 2013. Lymph node, T and B cell engraftment kinetics in a humanized mouse model: mature B-cells appear late and require T-cells for their development. J Immunol, 190(5):2090-101. PMID: 23335750. PMCID: PMC3578183. Highlighted “In This Issue” of JI (top 10% articles).

  • Rowland S.L., K. Tuttle, R.M. Torres, and R. Pelanda, 2013. Antigen and cytokine receptor signals guide the development of the naïve mature B cell repertoire. Immunologic Research, 55(1-3):231-40. PMID:22941591.

     

View of Recent Publications in PubMed

 


 

  

Julie Lang, Ph.D. (University of Colorado Denver)
Postdoctoral fellow

langj@njhealth.org

“Human B cell biology in humanized mice”

ChiaraBabolin.jpg

Chiara Babolin, Ph.D. (University of Padova, Italy)
Postdoctoral fellow

babolinc@njhealth.org

"Nature and role of tonic BCR signaling in immature B cell selection"

ChiaraBabolin.jpg

 
 
Allison Sang, Ph.D. (University of Florida)
Postdoctoral fellow
sanga@njhealth.org

"Dual antibody-expressing B cells in autoimmunity"
 


 

  

Margot Kelly, B.A. (University of Colorado, Boulder)
Lab Researcher II

kellym@njhealth.org

 







David Baldwin, B.S. (University of Colorado, Denver)
Lab Researcher I

baldwind@njhealth.org

 

 

Former lab members:

 

Corinne DePersis
Emilie Fournier
Regina Halverson
Jennifer Larson
Katelyn Leahy
Sucai Liu
Sarah Rowland
Lenka-Sinik Teodorovic
Sandra Thiemann
Maria-Gabriela (Gaby) Velez
Nick Weiss
 

Dr. Pelanda runs a joint lab together with Dr. Raul Torres.