Deciphering alternative functions of B lymphocytes

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B lymphocytes/cells are very important in the immune response and their main role is to produce antibodies. While the mechanisms regulating B lymphocyte activation leading to antibody production are well understood, those involved in key alternative B cell functions are poorly defined, particularly cytokine production and antigenic presentation. Also, B cells sometimes infiltrate tissues and form alternative lymphoid structures (ALS; normally found in specialized lymphoid organs) in response to various environmental stimuli (stress, inflammation, etc.), and the roles of ALS in normal tissues are unclear. ALS formation is a biological phenomenon, important for increasing the efficiency of microbe sampling by naive lymphocytes. To date, B lymphocytes have been studied mostly in animal models and need to be characterized in humans. Addressing this challenge represents the objective in the current NSERC proposal. Using previous NSERC funding, I established my program on B cell activation by several sources (CD40L/IL-4), which are normally received by activated T cells. Additionally, we have studied the importance of signals from microbiobes on B cells and have reported that some viral-based ligands trigger a process called autophagy, which in turn enhance antigenic presentation. We have performed transcriptomic profiling (evaluate the expression of all genes among the many 1000) from activated B cells, and from B cells isolated from ALS of the normal human kidney. We have defined 3 groups of genes, potentially involved in B cell activation and tissue-homing. Since the regulation of B lymphocyte tissue-homing-dependent functions in response to T cell and microbial signals is understudied, we will pursue the characterization of novel molecular events controlling alternative functions, specifically from tissue-resident and activated peripheral B cells. We hypothesize that programming of key B lymphocyte alternative functions is dictated by the response of B cell to environmental cues (activation/suppression) and to their anatomical localization. In this five-year short-term objectives, we propose to: AIM #1: Identify B cell subsets expressing modulated genes. AIM #2: Define the cytokine profile and capacity of antigenic presentation from the candidate genes AIM #3: Develop 3D culture system to better model normal B lymphocyte biology Impact of this research program So far, B cells have been studied mainly for antibody generation and diversity, and in their differentiation/development linked to antibody production. However, much remains to be understood in this specific field, especially in humans. We now know that B cells have key alternative functions such as antigenic presentation and immune modulation, both may be crucial in the control of immune responses. This project will focus on mechanisms controlling such essential alternative B cell functions.