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The Experimental Procedure of Somatic Hypermutation Analysis in Splenic B Cells During Primary Response

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Somatic hypermutation (SHM) is a critical process in adaptive immunity, enabling the generation of high-affinity antibodies through targeted mutations in immunoglobulin variable (IgV) regions. Here, we provide a comprehensive workflow combining immunization, molecular biology, and bioinformatics to investigate SHM mechanisms and outcomes. This is a general protocol for studying SHM at the VH186.2 region in C57BL/6 mice. While this method can be applied broadly, this chapter will detail the protocol used to test the effects of exonuclease 1(EXO1) knock-in mutation (Exo1D173A, or Exo1DA) or knock-out (KO) on hypermutation post-immunization by immunizing age-matched mice with NP(33)-CGG on alum. We start by immunizing and sacrificing the animals to obtain spleens for RNA extraction. We then create cDNA libraries and investigate VH186.2 region mutation to analyze SHM.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages493-499
Number of pages7
DOIs
StatePublished - 2026

Publication series

NameMethods in Molecular Biology
Volume2983
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • Activation-induced cytidine deaminase
  • Adaptive immunity
  • AID
  • B-cell receptor
  • BCR
  • Next-generation sequencing
  • Oncogenesis
  • SHM
  • Somatic hypermutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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