Analysis of somatic mutation and class switching in naive and memory B cells generating adoptive primary and secondary responses

Siekevitz, Miriam; Kocks, Christine; Rajewsky, Klaus; Dildrop, Renate

doi:10.1016/0092-8674(87)90073-0

Cited by 218 publications

(105 citation statements)

References 45 publications

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“…Included in this analysis is a panel of IgGl+ hybridomas derived from in vivo-activated B-cells (Siekevitz et al, 1987). Intra-intronic deletions accompany switch recombination For sorted IgGl+ cells of late activation phases we found the disappearance of the germline ctt EcoRI band from almost all IgH loci (Radbruch et al, 1986b).…”

Section: Discussionmentioning

confidence: 99%

Directed Ig class switch recombination in activated murine B cells.

Winter¹,

Krawinkel²,

Radbruch³

1987

The EMBO Journal

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Section: Discussionmentioning

confidence: 99%

Directed Ig class switch recombination in activated murine B cells.

Winter¹,

Krawinkel²,

Radbruch³

1987

The EMBO Journal

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“…It has been argued that a rate of 3 ϫ 10 Ϫ4 per base pair per generation is more accurate. Most calculated figures are, in fact, below 10 Ϫ4 (31,32). It is also worth remembering that the rate varies throughout the response, such that it is low to start with and increases at the height of the GC (33).…”

Section: ϫ4mentioning

confidence: 99%

Signals That Initiate Somatic Hypermutation of B Cells In Vitro

Bergthorsdottir

Gallagher

Jainandunsing

et al. 2001

The Journal of Immunology

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Somatic hypermutation is initiated as B lymphocytes proliferate in germinal centers. The signals that switch on the mutation process are unknown. We have derived an in vitro system to define signals that will initiate mutation in normal, naive splenic B cells. We find that three signals are required to allow detection of somatic mutation in vitro; these are anti-Ig, anti-CD40, and anti-CD38. If any one of these is omitted, mutation remains off. We show that CD40 is obligatory in vivo, as CD40 knockout mice exhibit no Ag-driven mutation. In contrast, CD38 is not, as CD38 knockout mice mutate normally. We believe that, in vitro, CD38, in combination with other stimuli, drives extensive cell division, allowing the detection of mutated sequences. However, in germinal centers in vivo, proliferative activity is instigated by a different molecule. This is the first demonstration of the initiation of hypermutation in vitro with normal splenic B cells using defined stimuli.

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“…Earlier work led to conflicting results as to whether memory B cells could accumulate further mutations [53][54][55].…”

Section: Discussionmentioning

confidence: 99%

Induction of somatic hypermutation by antigen‐specific B cell receptors in the human BL2 cell line

et al. 2004

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The role of the B cell antigen receptor in the induction of somatic hypermutation is presently unclear. We established stable transfectants of the human BL2 cell line expressing hen-egg lysozyme-specific IgM or IgA and compared their ability to induce somatic hypermutation of the endogenous rearranged heavy-chain gene. We found that IgM and IgA were both able to induce somatic hypermutation in an antigen dose-independent manner. The mutations displayed most of the characteristics of somatic hypermutation in vivo. Notably, some replacements introduced stop codons in the coding region. Our data suggest that class-switched memory B cells may undergo somatic hypermutation. They also suggest that the transmembrane/cytoplamic domains of the class-switched isotypes modulate the signaling and downmodulation activities of the BCR in an antigen dose-dependent manner.

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Analysis of somatic mutation and class switching in naive and memory B cells generating adoptive primary and secondary responses

Cited by 218 publications

References 45 publications

Directed Ig class switch recombination in activated murine B cells.

Directed Ig class switch recombination in activated murine B cells.

Signals That Initiate Somatic Hypermutation of B Cells In Vitro

Induction of somatic hypermutation by antigen‐specific B cell receptors in the human BL2 cell line

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