Structural differences between the repertoires of mouse and human germline genes and their evolutionary implications

Abstract

Although human and mouse antibodies are similar when one considers their diversification strategies, they differ in the extent to which kappa and lambda light chains are present in their respective variable light chain repertoires. While the Igk-V germline genes are preponderant in mice (95% or more), they comprise only 60% in humans. This may account for differences in the structural repertoire encoded in the Igk-V germline genes of these species. However, this subject has not been properly investigated, partially because a systematic structural characterization of the mouse Igk-V germline genes has not been undertaken. In the present study we compiled all available information on mouse Igk-V germline genes to characterize their structural repertoire. As expected, comparison with the structural repertoire of human Igk-V germline genes indicates differences. The most interesting is that the mouse Igk-V germline gene repertoire is more diverse in structural terms than its human counterpart: the mouse encodes seven canonical structure classes (combination of canonical structures in L1 and L3). In contrast, the human encodes only four. Analysis of the evolutionary relationships of human and mouse Igk-V germline genes led us to propose that the difference reflects a strategy of mice to compensate for the small lambda chain contribution to the repertoire of their variable light chains.

The functional repertoire of rabbit antibodies and antibody discovery via next-generation sequencing

“…Nonetheless, the repertoire of loop lengths at CDR-L1 is less diverse than its humans and mice counterpart, which encode for 7 and 5 lengths respectively and encompass more than two gene families. 25,26 Similar to the CDR-H3, the CDR-L3 length distribution does not differ in the BM, SP and IM samples. It is close to previous estimates 14 and follows a normal distribution with average lengths of 11.1 ± 1.1, 11.4 ± 1.1 and 11.1 ± 1.1 for the SP, BM and IM samples, respectively, and a range of 8 lengths having 8 to 15 amino acids.…”

Potential aggregation prone regions in biotherapeutics

“…κ light chains have a high abundance in mice (95%) but much lower (60%) in humans. 61 Sequence alignments for commercial mAbs. The multiple sequence alignment of light chains for commercial mAbs is presented in Figure 1A.…”

κ Editing Rescues Autoreactive B Cells Destined for Deletion in Mice Transgenic for a Dual Specific Anti-Laminin Ig

“…a L chains were assigned to V gene families based upon homology to published sequences (29) and using the nomenclature of the International ImMunoGeneTics database http://imgt.cnusc.fr;8104 (initiator and coordinator: M. P. Lefranc (30). J genes are assigned to known BALB/c J germline gene segments (31).…”

“…B, Predicted L chain V-J junction sequences and V gene segments used by the four mAb. L chains were sequenced by PCR amplification of DNA, as described in Materials and Methods, and assigned to V gene families based upon homology to published sequences (29) and using the nomenclature of the International ImMunoGeneTics database http:// imgt.cnusc.fr:8104 (initiator and coordinator: M.-P. Lefranc; e-mail address: lefranc@ligm.igh.cnrs.fr) (30). J genes are assigned to known BALB/c J germline gene segments (31).…”