Extrafollicular Activation of Lymph Node B Cells by Antigen-Bearing Dendritic Cells

TLDR

B lymphocytes recognize intact proteins rather than short peptides, but the site and mechanism by which unprocessed antigens become accessible to naïve B cells in lymph nodes remain unclear. Using two‑photon intravital imaging, the study shows that after exiting high‑endothelial venules, B cells survey dendritic cells before entering follicles. B‑cell receptor engagement of dendritic‑cell‑associated antigen induces calcium signaling, migration arrest, antigen acquisition, and extrafollicular accumulation, indicating a role for B‑DC interactions in promoting T‑cell‑dependent antibody responses.

Abstract

In contrast to naïve T cells that recognize short antigen-derived peptides displayed by specialized antigen-presenting cells, immunoglobulin receptors of B lymphocytes primarily recognize intact proteins. How and where within a lymph node such unprocessed antigens become available for naïve B cell recognition is not clear. We used two-photon intravital imaging to show that, after exiting high-endothelial venules and before entry into lymph node follicles, B cells survey locally concentrated dendritic cells. Engagement of the B cell receptor by the dendritic cell (DC)-associated antigen leads to lymphocyte calcium signaling, migration arrest, antigen acquisition, and extrafollicular accumulation. These findings suggest a possible role for antigen-specific B-DC interactions in promoting T cell-dependent antibody responses in vivo.