Embryogenesis of the bursa of Fabricius: stem cell, microenvironment, and receptor-paracrine pathways

The bursa of Fabricius is an ideal model system to answer the plethora of questions related to the origin of B cells and microenvironmental issues leading to the education of the stem cell. Prior to the 1960s, lymphocytes were thought to be derived from epithelial or mesenchymal cells. Later work demonstrated the bloodborne nature of the stem cell contributing to B cells. Stem cells entered the bursa of quail and chicken between 7 and 11 and 7.5 and 14 d of embryogenesis, respectively. Interspecific chimeric studies, quail and chick, emphasized the intraembryonic origin and sites of the stem cell. The bloodborne and stromal cells that contribute to the microenvironment of the bursa orchestrate the events leading to B cell differentiation. The separation of the endodermal and mesodermal components of the bursa revealed a singular role for the endoderm in the genesis of the bursa but did not exclude a role for the mesoderm. A dark mesenchymal cell was shown to play a role in bud formation. This cell gave rise to the bursal secretory dendritic cell (BSDC), unique in its membrane association with IgG. A receptor-paracrine thesis has been proposed to explain the interaction between in-frame B cells and Ig-positive BSDC in the expansion of in-frame B cells and the subsequent development of the B cell repertoire. Cell adhesion molecules have been integrated into this thesis.