Original Article

Immunoglobulin ß Signaling Regulates Locus Accessibility for Ordered Immunoglobulin Gene Rearrangements

Correspondence to: Hajime Karasuyama, 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. Tel:81-33-823-2101, ext. 5218 Fax:81-35-685-6608 E-mail: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 Igß 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 Igß 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 L chain germline transcription was found to be upregulated whereas the V_H 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 Igß 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

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