SαBP/BSAP/NF-Sμ B₁, a Murine and Human B Cell Stage Specific Nuclear Factor with DNA Binding Specificity Implying Roles in Switch-Recombination and Transcription

Abstract

Immunoglobulin genes undergo a programmed series of DNA rearrangements in B lymphoid cells. Following assembly of a functional variable (V) region gene, an independent series of recombinations determine the heavy chain isotype of the expressed antibody (IgM, IgG, IgE and IgA). Heavy chain class switches result in the deletion and replacement of the Cμ gene with a downstream C_H gene (Cℓ₃, Cℓ₁, Cℓ_2b, Cℓ_2a, C∈ or Cα) (reviewed in Marcu, 1982; Shimizu and Honjo, 1984; Radbruch et al., 1986; Gritzmacher, 1989). These recombinations are mediated by switch (S) regions which are positioned about 2 Kb 5’ of every C_H gene segment with the exception of Cδ. Differential regulation of C_H class switching is believed to be manifested by the accessibility of S segments to a B cell specific switch-recombinase activity (Stavnezer and Sirlin, 1986). Switch-recombination occurs at widely spaced positions within Sμ and other downstream S regions and only limited sequence homology between S sequences may be present near the site of recombination (Gritzmacher, 1989; Ott and Marcu, 1989). S regions consist of short tandemly repetitive sequences of varying length and homology which are believed to mediate switch recombination by an illegitimate mechanism. GAGCT and GGGGT sequences are found in all S regions in addition to three other commonly observed pentamers: ACCAG, GCAGC and TGAGC (reviewed in Shimizu and Honjo, 1984; Gritzmacher, 1989). A heptamer consensus motif, YAGGTTG (Y=pyrimidine), has also been found nearby a number of switch recombination sites in plasma cell tumors and hybridoma lines and is also repeated in various S segments (Marcu et al., 1982). The 5’ portion of the Sμ region is non-repetitive but does contain interspersed GAGCT, GGGGT and YAGGTTG like sequences while the 3’ portion is composed of a simple repetitive block of (GAGCT)_nGGGGT motifs where it ranges from one to seven (Nikaido et al., 1981). The Sμ, S∈ and Sα sequences display considerable homology particularly in areas containing repeats of GAGCT sequences while the Sℓ regions contain a lower density of these pentamers but are typified by 49mer or 52mer (Sℓ_2a) repeats and TGGGG, GCAGC and ACCAG motifs (Kataoka et al., 1981). The overall homology of the Sℓ regions correlates with their distance from SSμ (e.g., SSℓ₃> Sℓ₁> Sℓ_2b > Sℓ_2a) (shimizu et al., 1982; Stanton and Marcu 1982).