Figure 1. Immunoglobulin heavy chain locus and B cell development.

Schematic of the murine IgH locus showing variable (V_H, blue, n represents approximately 150 V_H gene segments), diversity (D_H, grey, n represents six to nine DSP gene segments), and joining (J_H, orange) gene segment [11],[12]. Exons encoding the constant regions of IgM and IgD are indicated as Cμ and Cδ. A promoter 5′ of DQ52, the 3′-most D_H gene segment, is indicated by the yellow oval and the intronic enhancer Eμ by a teal oval. Top line shows the germline (GL) configuration with associated histone modifications in B lineage precursors [23]–[25]. Histone H3 and H4 acetylation are shown in orange and presence of heterochromatic H3K9 methylation by the red line. Vertical red arrows represent the tissue-specific DNase I hypersensitive sites in the germline state. Next two lines show sequential stages of VDJ recombination at the IgH locus. D_H to J_H rearrangement occurs first resulting in a DJ_H junction and, depending on which D_H rearranges, residual upstream unrearranged D_Hs may be present. V_H rearrangement occurs to the DJ_H junction to generate a VDJ_H junction; during this process unrearranged D_Hs are lost from the genome.