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pre-BCR Library Construction

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Creative Biolabs offers our global customers a high diversity pre-BCR library generation service. Using our powerful Hi-Affi™ platform, we promise that the library diversity will be more than 1010 and the accuracy of library mutant will be 100%.

The pre-BCR (pre-B-cell receptor), also known as Surrobody, is transiently expressed during development of the antibody repertoire. The pre-BCR has a structure different from that of mature antibodies. It is a heterohexameric complex composed of identical pairs of heavy chains which are each paired with a two-subunit surrogate light chain (SLC). The SLC is a heterodimer composed of the noncovalently associated Vpre-B and λ5 proteins. The Vpre-B chain is homologous to a V Ig domain, and the λ5 chain is homologous to the C domain of canonical antibodies, respectively. Besides that, the SLC contains nonimmunoglobulin-like peptide extensions on each of the two components. This arrangement provides unique opportunities for protein engineering by functional derivatization of these nonimmunoglobulin-like tails. These tails can be easily fused with either a fully active cytokine or single-chain variable fragment (scFv) domains to generate pre-BCR with unique functions or pre-BCR that are bispecific with respect to targeted binding.

The pre-BCR has many unexampled excellent features which make them an attractive candidate for the construction of combinatorial libraries. First, it is derived from classical Ig domains, and thus one starts with structures that are homologous to the antibody. Second, the pre-BCR has more components rather than the classical antibodies, which should lend them to the construction of combinatorial protein libraries with large diversity. Such libraries, therefore, will exceed the diversity of antibody libraries: a combinatorial antibody library of 1.0×106 HCs and 1.0×106 light chains will yield a library of 1.0×1012 members, whereas a pre-BCR library of 1.0×106 HCs, 1.0×106 Vpre-B chains, and 1.0×106 λ5 chains will yield a library of 1.0×1018 members. Although the endogenous Vpre-B and λ5 chains are not inherently diverse, the unlimited diversity can be incorporated into the Vpre-B and λ5 chains by genetic engineering in much the same way as affinity maturation is accomplished for antibodies derived from combinatorial libraries.

The combinatorial pre-BCR libraries generated by our proprietary Hi-Affi™ phage display platform allow the synthesis and selection of very large numbers of specific binders in vitro. Such libraries, with the expected size of over 1010, can exceed the natural antibody repertoire and offer several advantages over conventional methods for finding antibodies. They allow access to rare specificities, can be fully human, and are not limited by systemic constraints such as immunological tolerance.

Creative Biolabs has been a long-term expert in the field of protein scaffold library construction. Our scientists take pride in having earned great reputation from our global clients by satisfactorily completed thousands of relevant projects in the past decade. We are confident in providing you with the best and most suitable service.


Fig. 1 Classical antibody versus Surrobody. (Haas 2008)

Reference
Haas, M. J. (2008) 'Surrogate antibodies', Science-Business eXchange, 1(28), http://www.nature.com/scibx/journal/v1/n28/pdf/scibx.2008.671.pdf.




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