Terminal deoxynucleotidyl transferase (TdT)-positive cells in human bo
ne marrow (BM) are a phenotypically inhomogeneous population of precur
sor cells. In their majority, these TdT(+) cells are unambiguously com
mitted to the B lineage, as evidenced by CD19 expression. However, TdT
(+) precursors that lack CD19 also exist and these may encompass a dif
ferentiation potential for the B as well as for other lineages. Becaus
e recent data suggested that CD19 expression is not the earliest diffe
rentiation event in B-cell ontogeny, we sought to reevaluate TdT(+) ly
mphoid precursors in pediatric BM to define the phenotypic denominator
of B-lineage affiliation upstream of CD19. Using four-color flow cyto
metry, we focused on the assessment of the CD79a antigen, which is hig
hly B-cell specific and which may also be expressed very early in B-ce
ll ontogeny. We found that a majority of TdT(+) cells coexpressed CD19
and CD79a in addition to CD10 and CD34, whereas, in all investigated
samples, some TdT(+) precursors lacked CD19 but expressed CD79a, which
suggestively indicates also their B-lineage affiliation. In contrast
to the CD19(+) precursors, which were usually CD10(hi) and CD79b(+), t
hese CD19(-)CD79a(+) putative B-cell precursors preferentially express
ed CD10 at row levels and were CD79b(+) in only 41%. About 17% of thes
e TdT(+)CD19(-)CD79a(+) precursors also coexpressed CD33 and CD7, but
not myeloperoxidase, CD14, or cytoplasmic CD3, which is discussed in t
he light of cellular activation rather than lineage promiscuity. Our d
ata confirm that the earliest differentiation stages of B cells can be
dissected upon expression of the lineage antigens CD79a and CD19 and
imply that CD79a is earlier expressed than CD19. This raises the chanc
e to follow the sequential events heralding B-cell commitment in the m
ost immature precursors by correlating phenotypic and genetic differen
tiation markers. (C) 1998 by The American Society of Hematology.