High affinity IgM+ memory B cells are generated through a germinal center-dependent pathway. Issue 2 (December 2015)

• Record Type: Journal Article
• Authors: Hara, Yasushi; Tashiro, Yasuyuki; Murakami, Akikazu; Nishimura, Miyuki; Shimizu, Takeyuki; Kubo, Masato; Burrows, Peter D.; Azuma, Takachika
• Is Part Of: Molecular immunology. Volume 68:Issue 2(2015:Dec.) Part C
• Page Start: 617
• Page End: 627
• Publication Date: 2015-12
• Subjects: Germinal center reaction -- Somatic hypermutation -- Class switch recombination -- Affinity maturation -- IgM; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2015.10.003
• Languages: English
• ISSNs: 0161-5890

Abstract

Graphical abstract: Highlights: Germinal center reaction in spleen. Active induction of somatic hypermutation in IgM. Down-regulation of class-switch recombination. Abstract: During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM + memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM + as well as IgG + memory B cells continued to be generated up to day 42. In contrast, class-switch recombination (CSR) was almost completed by day 7 and then the ratio of IgG1 + /IgM + GC B cells remained unchanged. Together these findings suggest that IgM + B cells undergo SHM in the GC to generate high affinity IgM + memory cells and that this process continues even after CSR is accomplished.