RESEARCH SUMMARY

B cells are essential effectors of the adaptive immune response to pathogens. They are responsible for pathogen neutralization and clearance through the production of antigen-specific antibodies. The prompt onset of the humoral immune response is thus crucial in the fight against invaders. This process depends critically on the ability of naïve B cells to search for antigen in secondary lymphoid organs (SLO).

Naive B cells migrate incessantly seeking for specific antigen in SLO. Once they enter lymph nodes through the high endothelial venules, B cells move towards the follicles, guided by the chemokine CXCL13 and a network of stromal cells. B cells explore the entire follicular volume, moving by random walking at an average speed of 6 µm/min. CXCL13, produced mainly by follicular dendritic cells, underlies this B cell behavior by signaling through its receptor, CXCR5. Specific antigen recognition through the B cell receptor (BCR) alters steady-state B cell dynamics at the follicle. B cells stop to gather antigen into a central cluster at the site of contact with the antigen-presenting cell, establishing an immune synapse. It is also possible that other stimuli, such as inflammatory and/or innate signals, modulate B cell dynamics and, thus, their function.

Therefore, modulation of B cell dynamics thus becomes critical for shaping the process of antigen encounter and subsequent B cell activation. Our goal is the study of the molecular mechanisms underlying the interplay between CXCR5 and the BCR or innate receptors and their effects on B cell dynamics and, ultimately, B cell fate. To do that, we have established a two-dimensional model that allows study of CXCL13-mediated B cell migration, antigen encounter and stimulation by other ligands in real time. We pursue a better understanding of the initial stages of the humoral immune response.