Mechanism and regulation of secondary immunoglobulin diversification

Cell Cycle. 2023 Sep;22(18):2070-2087. doi: 10.1080/15384101.2023.2275397. Epub 2023 Nov 23.

Abstract

Secondary immunoglobulin diversification by somatic hypermutation and class switch recombination in B cells is instrumental for an adequate adaptive humoral immune response. These genetic events may, however, also introduce aberrations into other cellular genes and thereby cause B cell malignancies. While the basic mechanism of somatic hypermutation and class switch recombination is now well understood, their regulation and in particular the mechanism of their specific targeting to immunoglobulin genes is still rather mysterious. In this review, we summarize the current knowledge on the mechanism and regulation of secondary immunoglobulin diversification and discuss known mechanisms of physiological targeting to immunoglobulin genes and mistargeting to other cellular genes. We summarize open questions in the field and provide an outlook on future research.

Keywords: Somatic hypermutation; germinal center; lymphomagenesis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes*
  • Cytidine Deaminase
  • Immunoglobulin Class Switching / genetics
  • Immunoglobulins* / genetics
  • Somatic Hypermutation, Immunoglobulin / genetics

Substances

  • Immunoglobulins
  • Cytidine Deaminase

Grants and funding

The work was supported by the Deutsche Forschungsgemeinschaft [JU2690/1-1 and 1-2, JU2690/4-1 and 4-2]; Deutsche Krebshilfe [70112155].