Deepta Bhattacharya
Associate Professor, BIO5 Institute
Associate Professor, Genetics - GIDP
Associate Professor, Immunobiology
Associate Professor, Surgery
Primary Department
Department Affiliations
(520) 626-8088
Research Interest
Research in the Bhattacharya lab focuses on molecular approaches to direct B cell differentiation to establish immunity to infectious disease, and stem cell differentiation for regenerative medicine. Current projects in the lab include: 1) Understanding the cellular basis of antibody-mediated immunity to variable viruses. After infection or vaccination, B cells that recognize the pathogen proliferate and undergo a massive level of expansion. Upon clearance of the infection a small fraction of the "best" B cells are retained to become memory B cells or long-lived plasma cells. Our recent work has established that memory B cells are excellent at recognizing not only the original pathogen, but also mutant escape variants of the pathogen. In contrast, long-lived plasma cells are highly specific only for the original pathogen. We are studying the transcription factors that regulate the memory B cell vs. long-lived plasma cell fate, and are studying mechanisms to alter this fate to provide effective immunity against mutable viruses such as influenza and Dengue. 2) Identifying molecular regulators of the duration of immunity. Most clinically used vaccines rely on the production of antibodies to confer immunity. The duration of immunity can vary greatly between different vaccines, yet the molecular basis of this remains unknown. Current efforts are focused on the identification of genes that regulate plasma cell lifespan and on the features of the vaccine that confer durable antibody immunity. 3) Engineering human pluripotent stem cells to generate antibody-mediated immunity. A small fraction of patients infected with HIV or dengue virus, or vaccinated against influenza develop remarkable antibodies that neutralize nearly all clinical isolates of these viruses. Yet it is unclear how to induce these types of antibodies in the broader population through standard vaccination. Using novel targeted nuclease technologies, we are engineering human embryonic stem cells to express these antibodies and differentiating them into transplantable long-lived plasma cells. The long-term goal of this project is to provide permanent immunity to recipients of these engineered plasma cells.


Beerman, I., Bhattacharya, D., Zandi, S., Sigvardsson, M., Weissman, I. L., Bryder, D., & Rossi, D. J. (2010). Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proceedings of the National Academy of Sciences of the United States of America, 107(12), 5465-70.

Aging of the hematopoietic stem cell compartment is believed to contribute to the onset of a variety of age-dependent blood cell pathophysiologies. Mechanistic drivers of hematopoietic stem cell (HSC) aging include DNA damage accumulation and induction of tumor suppressor pathways that combine to reduce the regenerative capacity of aged HSCs. Such mechanisms do not however account for the change in lymphoid and myeloid lineage potential characteristic of HSC aging, which is believed to be central to the decline of immune competence and predisposition to myelogenous diseases in the elderly. Here we have prospectively isolated functionally distinct HSC clonal subtypes, based on cell surface phenotype, bearing intrinsically different capacities to differentiate toward lymphoid and myeloid effector cells mediated by quantitative differences in lineage priming. Finally, we present data supporting a model in which clonal expansion of a class of intrinsically myeloid-biased HSCs with robust self-renewal potential is a central component of hematopoietic aging.

Bhattacharya, D., Lee, D. U., & Sha, W. C. (2002). Regulation of Ig class switch recombination by NF-kappaB: retroviral expression of RelB in activated B cells inhibits switching to IgG1, but not to IgE. International immunology, 14(9), 983-91.

Mutant NF-kappaB-deficient B cells from knockout mice lacking RelA, p105/p50 or the transactivation domain of c-Rel exhibit distinct and selective cell-intrinsic defects in their ability to undergo class switch recombination (CSR) to specific Ig isotypes. This isotype-specific requirement for particular NF-kappaB transcription factors in B cells activated to undergo CSR is intriguing because the NF-kappaB composition in B cells is also highly regulated and can vary significantly depending upon how B cells are activated. These studies prompted us to test by retroviral transduction of normal B cells whether changes in the NF-kappaB composition in activated B cells could modulate cytokine-driven CSR. RelB, RelA, c-Rel, p50 and p52 were first expressed in lipopolysaccharide-activated primary B cells and then induced by cytokine addition to undergo CSR to IgG1, IgE, IgG2a, IgG2b or IgA. Surprisingly, only retroviral expression of RelB altered CSR, resulting in a 3-fold decrease in CSR to IgG1 induced by IL-4. This effect was isotype specific as RelB expression did not affect CSR to IgE within the same culture or to other isotypes tested. The transactivation domain of RelB was required for inhibition of CSR to IgG1. Expression of p50-RelB or p52-RelB dimers joined covalently by a flexible peptide linker also specifically inhibited IgG1 CSR. RelB-mediated inhibition of IgG1 CSR was associated with a decrease in germline gamma1 transcription, but not with changes in proliferation as assayed by CFSE labeling. Thus, RelB complexes can specifically inhibit CSR to IgG1, but not IgE, in activated, primary B cells.

Bhattacharya, D., & Wong, R. (2016). The Chosen Few: Only a Subset of Memory B Cells Responds to Secondary Dengue Virus Infections. EBioMedicine, 12, 12-13.
Sandoval, G. J., Graham, D. B., Bhattacharya, D., Sleckman, B. P., Xavier, R. J., & Swat, W. (2013). Cutting edge: cell-autonomous control of IL-7 response revealed in a novel stage of precursor B cells. Journal of immunology (Baltimore, Md. : 1950), 190(6), 2485-9.

During early stages of B-lineage differentiation in bone marrow, signals emanating from IL-7R and pre-BCR are thought to synergistically induce proliferative expansion of progenitor cells. Paradoxically, loss of pre-BCR-signaling components is associated with leukemia in both mice and humans. Exactly how progenitor B cells perform the task of balancing proliferative burst dependent on IL-7 with the termination of IL-7 signals and the initiation of L chain gene rearrangement remains to be elucidated. In this article, we provide genetic and functional evidence that the cessation of the IL-7 response of pre-B cells is controlled via a cell-autonomous mechanism that operates at a discrete developmental transition inside Fraction C' (large pre-BII) marked by transient expression of c-Myc. Our data indicate that pre-BCR cooperates with IL-7R in expanding the pre-B cell pool, but it is also critical to control the differentiation program shutting off the c-Myc gene in large pre-B cells.

He, Z., O'Neal, J., Wilson, W. C., Mahajan, N., Luo, J., Wang, Y., Su, M. Y., Lu, L., Skeath, J. B., Bhattacharya, D., & Tomasson, M. H. (2016). Deletion of Rb1 induces both hyperproliferation and cell death in murine germinal center B cells. Experimental hematology, 44(3), 161-5.e4.

The retinoblastoma gene (RB1) has been implicated as a tumor suppressor in multiple myeloma (MM), yet its role remains unclear because in the majority of cases with 13q14 deletions, un-mutated RB1 remains expressed from the retained allele. To explore the role of Rb1 in MM, we examined the functional consequences of single- and double-copy Rb1 loss in germinal center B cells, the cells of origin of MM. We generated mice without Rb1 function in germinal center B cells by crossing Rb1(Flox/Flox) with C-γ-1-Cre (Cγ1) mice expressing the Cre recombinase in class-switched B cells in a p107(-/-) background to prevent p107 from compensating for Rb1 loss (Cγ1-Rb1(F/F)-p107(-/-)). All mice developed normally, but B cells with two copies of Rb1 deleted (Cγ1-Rb1(F/F)-p107(-/-)) exhibited increased proliferation and cell death compared with Cγ1-Rb1(+/+)-p107(-/-) controls ex vivo. In vivo, Cγ1-Rb1(F/F)-p107(-/-) mice had a lower percentage of splenic B220+ cells and reduced numbers of bone marrow antigen-specific secreting cells compared with control mice. Our data indicate that Rb1 loss induces both cell proliferation and death in germinal center B cells. Because no B-cell malignancies developed after 1 year of observation, our data also suggest that Rb1 loss is not sufficient to transform post-germinal center B cells and that additional, specific mutations are likely required to cooperate with Rb1 loss to induce malignant transformation.