Ligation of Surface Ig by Gut-Derived Antigen Positively Selects Chicken Bursal and Peripheral B Cells

Abstract

In many mammals and birds, B cell lymphopoiesis takes place in GALT, such as the avian bursa of Fabricius. Although BCR expression is sufficient for bursal colonization, the role of BCR ligation in the later stages of bursal B cell lymphopoiesis remains elusive. To address this directly, we introduced a surface Ig-related construct with defined Ag specificity containing the Ag-binding portion of a lamprey variable lymphocyte receptor specific for PE fused to a truncated chicken μ-chain (VLR(PE)Tμ) into developing chick embryos. VLR(PE)Tμ expression supports bursal follicle colonization, clonal expansion, and Ig V gene diversification. VLR(PE)Tμ-expressing B cells migrate to the periphery in the absence of the Ag starting from day 18 of embryogenesis. VLR(PE)Tμ-expressing B cells declined rapidly in the bursa and periphery in the absence of Ag after hatch; however, intrabursal injection of PE prolonged survival of VLR(PE)Tμ(+) bursal and peripheral B cells. Intrabursal introduction of Ag increased emigration of short-lived LT2(+) B cells. Peripheral VLR(PE)Tμ(+) B cells were maintained following intrabursal PE application and contained both short-lived LT2(+) and long-lived LT2(-) B cells. In the chicken bursa, the later stages of B cell development occur in the presence of gut-derived Ag; therefore, we conclude that Ag-mediated ligation of BCR in bursal B cells acts to positively select bursal B cells into both short-lived and long-lived peripheral B cell populations.