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The Extent of Histone Acetylation Correlates with the Differential Rearrangement Frequency of Individual V_H Genes in Pro-B Cells¹

Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

During B lymphocyte development, Ig heavy and L chain genes are assembled by V(D)J recombination. Individual V, D, and J genes rearrange at very different frequencies in vivo, and the natural variation in recombination signal sequence does not account for all of these differences. Because a permissive chromatin structure is necessary for the accessibility of V_H genes for V_H to DJ_H recombination, we hypothesized that gene rearrangement frequency might be influenced by the extent of histone modifications. Indeed, we found in freshly isolated pro-B cells from µMT mice a positive correlation between the level of enrichment of V_HS107 genes in the acetylated histone fractions as assayed by chromatin immunoprecipitation, and their relative rearrangement frequency in vivo. In the V_H7183 family, the very frequently rearranging V_H81X gene showed the highest association with acetylated histones, especially in the newborn. Together, our data show that the extent of histone modifications in pro-B cells should be considered as a mechanism by which accessibility and the rearrangement level of individual V_H genes is regulated.

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