Somatic hypermutation

Somatic hypermutation is a process that allows B cells to mutate the genes that they use to produce antibodies. This enables the B cells to produce antibodies that are better able to bind to bacteria, viruses and other infections.

Latest Research and Reviews

  • Reviews |

    Diversification of the antibody repertoire is well known to be driven by genetic recombination and mutation. However, it is becoming apparent that other processes can also diversify antibody specificities. Here, Dimitrov and colleagues discuss these unconventional strategies for antibody diversification and consider why these extra strategies have evolved.

    • Alexia Kanyavuz
    • , Annaelle Marey-Jarossay
    • , Sébastien Lacroix-Desmazes
    •  & Jordan D. Dimitrov
  • Research | | open

    Knowledge on how antibody responses have evolved is critical for the induction of protective immunity. Here the authors analyse, using high-throughput sequencing of both exon and intron regions, the mutation and lineage development of an HIV-neutralizing antibody to find an unexpected early emergence of broadly neutralizing species.

    • Erik L. Johnson
    • , Nicole A. Doria-Rose
    • , Jason Gorman
    • , Jinal N. Bhiman
    • , Chaim A. Schramm
    • , Ashley Q. Vu
    • , William H. Law
    • , Baoshan Zhang
    • , Valerie Bekker
    • , Salim S. Abdool Karim
    • , Gregory C. Ippolito
    • , Lynn Morris
    • , Penny L. Moore
    • , Peter D. Kwong
    • , John R. Mascola
    •  & George Georgiou
  • Research | | open

    Activation-induced deaminase (AID) is important for inducing desirable mutations at the B cell receptor genes for effective antibody responses. Here the authors show that three key arginine residues of AID link AID-chromatin association with transcription elongation to license AID for specific mutagenesis in B cells.

    • Stephen P. Methot
    • , Ludivine C. Litzler
    • , Poorani Ganesh Subramani
    • , Anil K. Eranki
    • , Heather Fifield
    • , Anne-Marie Patenaude
    • , Julian C. Gilmore
    • , Gabriel E. Santiago
    • , Halil Bagci
    • , Jean-François Côté
    • , Mani Larijani
    • , Ramiro E. Verdun
    •  & Javier M. Di Noia
  • Research | | open

    Somatic hypermutation of antibodies can occur in infants but are difficult to track. Here the authors present a new method called MIDCIRS for deep quantitative repertoire sequencing with few cells, and show infants as young as 3 months can expand antibody lineage complexity in response to malaria infection.

    • Ben S. Wendel
    • , Chenfeng He
    • , Mingjuan Qu
    • , Di Wu
    • , Stefany M. Hernandez
    • , Ke-Yue Ma
    • , Eugene W. Liu
    • , Jun Xiao
    • , Peter D. Crompton
    • , Susan K. Pierce
    • , Pengyu Ren
    • , Keke Chen
    •  & Ning Jiang
  • Research |

    B-cell VH region repertoire sequencing of eight anatomical sites in six human donors reveals distinct networks of clone distribution.

    • Wenzhao Meng
    • , Bochao Zhang
    • , Gregory W Schwartz
    • , Aaron M Rosenfeld
    • , Daqiu Ren
    • , Joseph J C Thome
    • , Dustin J Carpenter
    • , Nobuhide Matsuoka
    • , Harvey Lerner
    • , Amy L Friedman
    • , Tomer Granot
    • , Donna L Farber
    • , Mark J Shlomchik
    • , Uri Hershberg
    •  & Eline T Luning Prak
    Nature Biotechnology 35, 879-884

News and Comment

  • News and Views |

    How B cell tolerance is retained during somatic hypermutation in germinal centers is incompletely understood. Two studies now show that Foxp3+ regulatory T cells undergo functional specialization to limit the magnitude of the germinal center response, and they may contribute to our understanding of how germinal center–mediated autoimmunity is prevented (pages 975–982 and 983–988).

    • Daniel J Campbell
    •  & Meghan A Koch
    Nature Medicine 17, 929-930
  • News and Views |

    Direct evaluation of the contribution of somatic hypermutation (SHM) to mucosal immunity has been hampered by the lack of models able to dissociate SHM from class-switch recombination, which are both dependent on the cytidine deaminase AID. A new mouse AID model now demonstrates the critical role of SHM in the control of gut bacteria.

    • Kang Chen
    •  & Andrea Cerutti
    Nature Immunology 12, 197-198