Development of the expressed immunoglobulin μ chain repertoire during maturation of mice B cells

Abstract

In the bone marrow and spleen, the developing B cell populations undergo both negative and positive selections to shape their B cell receptor repertoire. To gain insight into the shift of the immunoglobulin heavy (IgH) chain repertoire during B cell development, we undertook large scale Ig μ chain repertoire analysis of pre-B, immature B and spleen B cell populations. We found that the majority of V_H gene segments, V_H families, J_H and D gene segments, were observed to have significantly different usage frequencies when three B cell populations were compared, but the usage profile of the V_H, D, and J_H genes between different B cell populations showed high correlations. In both productive and nonproductive rearrangements, the length of CDRH3 shortened significantly on average when B cells entered the periphery. However, the CDRH3 length distribution of nonproductive rearrangements did not follow a Gaussian distribution, but decreased successively in the order 3n-2, 3n-1 and 3n, suggesting a direct correlation between mRNA stability and CDRH3 length patterns of nonproductive rearrangements. Further analysis of the individual components comprising CDRH3 of productive rearrangements indicated that the decrease in CDRH3 length was largely due to the reduction of N addition at the 5′ and 3′ junctions. Moreover, with development, the amino acid content of CDRH3 progressed toward fewer positively charged and nonpolar residues but more polar residues. All these data indicated that the expressed Ig μ chain repertoire, especially the repertoire of CDRH3, was fine-tuned when B cells passed through several checkpoints of selection during the process of maturation.

Keywords

immunoglobulin / heavy chain / variable region / repertoire / complementarity determining region 3 of the IgH chain (CDRH3)

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Acknowledgements

This work was supported by the National Basic Research Program of China (2010CB945300).

Supplementary materials

The online version of this article at http://dx.doi.org/10.15302/J-FASE-2014017 contains supplementary materials (Appendix).

Compliance with ethics guidelines

Jingwen Liang, Yingfeng Luo, Yi Sun, Meng Lei, Bing Zhang, Songnian Hu and Yaofeng Zhao declare that they have no conflict of interest or financial conflicts to disclose.

All applicable institutional and national guidelines for the care and use of animals were followed.

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Higher Education Press and Springer-Verlag Berlin Heidelberg