Profilbild von Dr. Palash Maity

Dr. Palash Maity

Postdoctoral Research Scientist

Focus of Research

The primary functionality of the adaptive immune system is to deliver specifically protective antibodies those are produced and secreted by B-lymphocytes (B cells). While a single B cell and its progenitor eventually expresses a unique specificity of antibody through recombination of immunoglobulin (Ig) gene segments, the process itself generates a diversified pool of B cells carrying varieties of specificities.  These antibodies in their membrane-bound form remain anchored on the plasma membrane and serve as signal transducing B cell antigen receptors (BCRs), which transmit signals for survival, proliferation, and differentiation of B cells. Despite having the same specificity, a naïve B cell express different BCR isotypes, namely IgM and IgD, on their surface. For obvious reason, the functional difference and correlation between IgM and IgD-BCRs had drawn an early attention, however, it remained obscure for a long time. Our recent study revealed that the IgM and IgD-BCRs form independent nanoclusters and reside in separate protein islands on plasma membrane, thereby facilitating the independent initiation of IgM and IgD specific signaling. Furthermore, the receptor members of a protein islands also have functional implications. Our study elucidated that the IgD-BCR, CD19 and the CXCR4 chemokine receptor are close neighbors and that the IgD-BCR and CD19 are required for CXCR4 to function. We also propose a central role for the cytoskeleton in the communication between receptors, those are not only important for basic research but also for applied clinical science.

We are interested in decrypting the association and functional role of co-receptors such as CXCR4 and IGFR1 involved in membrane organization together with BCR isotypes in different healthy B cells subsets and B cell neoplasms such as Chronic Lymphocytic Leukemia (CLL), Diffuse large B-cell lymphoma (DLBCL) and Splenic B-cell lymphoma/leukemia. In cooperation with Prof. Jumaa group, we investigate the functional association of several CLL derived BCRs with CXCR4 in reconstitution studies. We also aim to translate the efficacy of potential blockers of these co-receptors signaling in clinical settings.

We are interested to investigate the cooperation of different co-receptors in IgM and IgD-BCR islands on B cell development, survival, homing and response to immunization. Using genetically modified mouse models for IgM and IgD we study the role of co-receptors namely CD19 and CXCR4 in B cell fitness in vivo.  Together with Prof. M. Reth and support from TRR130 consortium, we would like to develop an inducible IgD deletion system, especially to understand the role of IgD protein island in B cell function.

We are interested in the role of chemokine-driven migration and cytoskeleton remodeling of B cell during activation of competent B cells during immunization.  Using transgenic mouse models and inducible deletion system, we study the homing of B cells into niches during activation in response to antigen.

Becker, M., Hobeika, E., Jumaa, H., Reth, M., Maity, P. C.. 2017. CXCR4 signaling and function require the expression of the IgD-class B-cell antigen receptor. Proc Natl Acad Sci USA 114(20): 5231-5236.

Hobeika, E., Maity, P. C., Jumaa, H. 2016. Control of B cell responsiveness by the isotype and structural elements of the antigen receptor. Trends Immunol 37(5):  310-320.

Maity, P. C., Blount, A, Jumaa, H., Ronneberger, O., Lillemeier, B. F., Reth, M.. 2015. B cell antigen receptors of class IgM and IgD are clustered in different protein islands that are altered during B cell activation.  Science Signal 8: ra93.

Maity, P. C., Yang, J., Klaesener, K., Reth, M. 2014. The nanoscale organization of the B lymphocyte membrane. Biochim Biophys Acta 1853: 830-840. 

Klasener K, Maity P.C., Hobeika E, Yang J, Reth M. 2014. B cell activation involves nanoscale receptor reorganizations and inside-out signalying by Syk. Elife3. E02069.

Maity, P. C., Ray, T., Das, B. & Sil, A. K. 2012. IKKbeta-I-kappaBvarepsilon-c-Rel/p50: a new axis of NF-kappaB activation in lung epithelial cells. Oncogenesis 1, e8.