Ordering of human bone marrow B lymphocyte precursors by single-cell polymerase chain reaction analyses of the rearrangement status of the immunoglobulin H and L chain gene loci

Paolo Ghia, Edwin Ten Boekel, Eva Sanz, Antonio De La Hera, Antonius Rolink, Fritz Melchers

Research output: Contribution to journalArticle


CD19+CD10+ human B lineage bone marrow cells were separated into cycling or resting cells, which differ in their expression of CD34, V(preB), recombination activating gene (RAG-1), and terminal deoxynucleotidyl transferase (TdT). Polymerase chain reaction analyses developed for D(H)J(H) and V(K)J(K) V(K)J(K)K((de)) and V(K)K((de)) rearrangements with DNA of single cells and a comparison with B lineage cell development in mouse bone marrow, allow to delineate the human B lymphocyte pathway of development as follows: CD34+V(preB)+RAG-1+TdT+, D(H)J(H)-rearranged, KL germline cycling pre-B I cells → CD34- V(preB)+μH chain+ (pre-B receptor+) RAG- 1+ TdT, V(H)D(H)J(H)-rearranged, KL germline, cycling pre-B II cells → CD34- V(preB)-, intracytoplasmic μH chain+ (pre-B receptor) RAG-1+ TdT, V(H)D(H)J(H)-rearranged, mainly KL germline cycling pre-B II cells → CD34+ V(preB)- intracytoplasmic μH chain+, RAG-1+ TdT, V(H)D(H)J(H)-rearranged, V(K)J(K)-rearranged, IgM-, resting pre-B II cells → CD34+ V(preB)-, sIgM+, RAG-1+ TdT-, V(H)D(H)J(H)- and V(K)J(K)-rearranged IgM+ immature B cells → CD34+, CD10- sIgM+/sIgD+ mature B cells. This order, for the first time established for human B lineage cells, shows striking similarities with that established for mouse B lineage cells in bone marrow.

Original languageEnglish
Pages (from-to)2217-2229
Number of pages13
JournalJournal of Experimental Medicine
Issue number6
Publication statusPublished - Dec 1 1996


ASJC Scopus subject areas

  • Immunology

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