Commitment to the B Lymphoid Lineage Occurs before D_H-J_H Recombination

Lineage commitment in B lymphopoiesis remains poorly understood due to the inability to clearly define newly committed B lineage progenitors and their multipotential descendants. We examined the potential of three recently described progenitor populations in adult mouse bone marrow to differentiate into each hematopoietic lineage. The earliest of these, termed fraction (Fr.) A₀, exhibited myeloid, erythroid, and B and T lymphoid progenitor activity and included individual cells with myeloid/B lymphoid potential. In sharp contrast, two later populations, termed Frs. A₁ and A₂ and characterized by surface B220 expression and transcription of the germline immunoglobulin heavy chain (IgH) locus, lacked progenitor activity for all hematopoietic lineages except B lymphocytes. These observations, together with single cell polymerase chain reaction analysis showing a lack of D_HJ_H rearrangements in each population and experiments showing identical precursor potentials when these populations were derived from recombination activating gene (Rag)-1^−/− and J_H^−/− mice, demonstrate that commitment to the B lymphoid lineage occurs before and independently of V_HD_HJ_H recombination.