Elsevier

Immunobiology

Volume 198, Issues 1–3, December 1997, Pages 227-235
Immunobiology

Essential Functions of Pax-5 (BSAP) in pro-B Cell Development

https://doi.org/10.1016/S0171-2985(97)80043-5Get rights and content

Abstract

Pax-5 codes for the transcription factor BSAP which is expressed in all B-lymphoid tissues inaddition to the developing central nervous system and testis. Within the B-lymphoid lineage, Pax-5 expression is already detected in the earliest B cell progenitors and persists up to the mature B cell stage. Targeted inactivation of the Pax-5 gene in the mouse germline revealed a differential dependency of fetal and adult B-lymphopoiesis on this transcription factor. Pax-5 is required for the differentiation of the earliest B-lineage-committed precursor cells in the fetal liver. In contrast, B cell development in the adult bone marrow progresses up to an early pro-B cell stage in the absence of Pax-5 function. The expression of CD19, Igα (Mb-1) and N-myc is severely, reduced in Pax-5-deficient pro-B cells. These BSAP target genes are, however, unlikely to explain the early developmental block based on their known function in B cell development. Moreover, VH-to-DIIJII rearrangements at the immunoglobulin heavy-chain locus are ∼50-fold reduced in Pax-5-deficient pro B-cells, while the DII-to-JH rearrangements occur at a normal frequency. However, the expression of rearranged μ heavy-chain transgenes does not allow Pax-5-deficient pro-B cells to develop further to the pre-B cell stage. Together these data demonstrate therefore that B cell development in the Pax-5 deficient bone marrow is arrested at an early pro-B cell stage which is not yet responsive to pre-B cell receptor signaling.

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    Dr. M. Busslinger, Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A - 1030 Vienna, Austria, Tel.: (+43/1) 797 30-452, Fax: (+43/1) 798 71 53

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