During the 2009 fiscal year, we accomplished the following: 1. Completed the first phase of analysis of pulsed-BCR signaling in splenic B cells. We found that a single round of BCR signaling primed cells to receive T cell help by: i) secreting T cell attracting chemokines CCL3 and CCL4; ii) up-regulating the chemokine receptor CCR7 that facilitates B cell migration to T cell zones; iii) up-regulating MHC II surface expression;and iv) increasing the sensitivity to CD40 signals. 2. The basis for hyper-responsiveness to CD40 was proposed to be due to down-regulation of the adapter molecule, BANK, which is a negative regulator of CD40. In addition, CD40 responsiveness was reduced in c-Rel-deficient B cells indicating that a part of the priming effect was mediated via this NF-kB family member. 3. Initiated a collaboration with Dr. Mark Shlomchik to determine whether pulse activation occurs during in vivo immunization. Enroute to the in vivo experiment, we showed that antigen-specific priming occurs in vitro. 4 Completed the first phase of analysis of the function of two phases of c-Rel induction in BCR-activated spleen B cells in collaboration with Dr. Steve Gerondakis. We found that phase l c-Rel induces A1 gene expression and phase 2 c-Rel induces Bcl-XL gene expression. Both A1 and Bcl-XL were found to be important to maintain B cell viability after BCR cross-linking.
| Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako et al. (2016) Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers. J Immunol 196:3385-97 |
| Kaileh, Mary; Vazquez, Estefania; MacFarlane 4th, Alexander W et al. (2016) mTOR-Dependent and Independent Survival Signaling by PI3K in B Lymphocytes. PLoS One 11:e0146955 |
| Fowler, Trent; Garruss, Alexander S; Ghosh, Amalendu et al. (2015) Divergence of transcriptional landscape occurs early in B cell activation. Epigenetics Chromatin 8:20 |
| Maul, Robert W; Cao, Zheng; Venkataraman, Lakshmi et al. (2014) Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo-activated cells. J Exp Med 211:2297-306 |
| Kaileh, Mary; Sen, Ranjan (2012) NF-ýýB function in B lymphocytes. Immunol Rev 246:254-71 |
| Sen, Ranjan (2011) The origins of NF-?B. Nat Immunol 12:686-8 |
| Olkhanud, Purevdorj B; Damdinsuren, Bazarragchaa; Bodogai, Monica et al. (2011) Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4? T cells to T-regulatory cells. Cancer Res 71:3505-15 |
| Fowler, Trent; Sen, Ranjan; Roy, Ananda L (2011) Regulation of primary response genes. Mol Cell 44:348-60 |
| Damdinsuren, Bazarragchaa; Zhang, Yongqing; Khalil, Ashraf et al. (2010) Single round of antigen receptor signaling programs naive B cells to receive T cell help. Immunity 32:355-66 |
| Sen, Ranjan; Smale, Stephen T (2010) Selectivity of the NF-{kappa}B response. Cold Spring Harb Perspect Biol 2:a000257 |
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