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DEPARTMENT OF IMMUNOLOGY & MICROBIOLOGY, A Leader in Immunology, Microbiology and Microbial Pathogenesis Research and Training

Immunology and Microbiology
 

Roberta Pelanda, Ph.D.

Professor of Immunology & Microbiology


12800 E. 19th Eve., RC1-N 8104
Mail Stop 8333, Aurora, CO 80045

Phone: 303-724-8666
E-mail: Roberta.Pelanda@ucdenver.edu

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.



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

langj@njhealth.org

“Human B cell biology in humanized mice”



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"



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.


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