The neuro-B cell link of peptidergic innervation in the Bursa Fabricii

The Bursa Fabricii, restricted to birds, specifically provides the microenvironment for B-cell maturation. The presence of nerve fibers containing immunopotent neuropeptides in immune organs opens interesting perspectives on the understanding of neuroimmune communication. As an organ for the development of only B-lymphocytes is not known in mammals, the contribution of a peptidergic innervation to the microenvironment of B-cells is not known. Therefore, we studied the peptidergic innervation of the Bursa Fabricii as an organ of B-cell maturation. Four different neuropeptides were found in nerve fibers of the Bursa Fabricii: tachykinins (TK), vasoactive intestinal peptide (VIP), galanin (GAL), and calcitonin gene-related peptide (CGRP). All these neuropeptides were distributed throughout the different bursal compartments, with the exception of the medulla of the bursal follicles, where the early stages of lymphocyte maturation are found. Double immunofluorescent studies revealed three different fiber populations: One containing coexisting VIP and GAL, the second TK and CGRP, and the last TK and no CGRP. Some of the TK-ir fibers may contain coexisting VIP. As demonstrated by double labeling for neuropeptides and lymphocytes, these heterologous fiber populations were found adjacent to B-cells in the follicle cortex. In addition, VIP-ir fibers were seen in association with macrophages. The origins of the fiber populations and the possible functional implications of our findings are discussed.