The Journal of Experimental Medicine
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Published online 17 April 2000.
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© The Rockefeller University Press, 0022-1007/2000/4/1333/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 8, April 17, 2000 1333-1340

Original Article

Immunoglobulin β Signaling Regulates Locus Accessibility for Ordered Immunoglobulin Gene Rearrangements

Kazushige Makia, Kisaburo Nagataa, Fujiko Kitamuraa, Toshitada Takemorib, and Hajime Karasuyamaa

a Department of Immunology, Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan
b Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Department of Immunology, Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.81-35-685-660881-33-823-2101, ext. 5218

h-karas{at}rinshoken.or.jp

The antigen receptor gene rearrangement at a given locus is tightly regulated with respect to cell lineage and developmental stage by an ill-defined mechanism. To study the possible role of precursor B cell antigen receptor (pre-BCR) signaling in the regulation of the ordered immunoglobulin (Ig) gene rearrangement during B cell differentiation, a newly developed system using µ heavy (H) chain membrane exon (µm)-deficient mice was employed. In this system, the antibody-mediated cross-linking of Igβ on developmentally arrested progenitor B (pro-B) cells mimicked pre-BCR signaling to induce early B cell differentiation in vivo. Analyses with ligation-mediated polymerase chain reaction revealed that the Igβ cross-linking induced the redirection of Ig gene rearrangements, namely, the suppression of ongoing rearrangements at the H chain locus and the activation of rearrangements at the light (L) chain locus. Upon the cross-linking, the {kappa}L chain germline transcription was found to be upregulated whereas the VH germline transcription was promptly downregulated. Notably, this alteration of the accessibility at the H and L chain loci was detected even before the induction of cellular differentiation became detectable by the change of surface phenotype. Thus, the pre-BCR signaling through Igβ appears to regulate the ordered Ig gene rearrangement by altering the Ig locus accessibility.

Key Words: pre–B cell receptor • surrogate light chain • allelic exclusion • B cell development • recombinase

Abbreviations used in this paper: APC, allophycocyanin; BCR, B cell antigen receptor; HPRT, hypoxanthine phosphoribosyl transferase; LMPCR, ligation-mediated PCR; pre-B, precursor B; pro-B, progenitor B; RAG, recombination activating gene; RSS, recombination signal sequence; RT, reverse transcription.

© 2000 The Rockefeller University Press


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