Intraclonal generation of antibody mutants in germinal centres

Jacob, Joshy; Kelsoe, Garnett; Rajewsky, Klaus; Weiß, Ursula

doi:10.1038/354389a0

Cited by 1,006 publications

(751 citation statements)

References 22 publications

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“…Upon contact with antigen surface IgD þ B lymphocytes of the follicular mantle give rise to primary B cell blasts that colonize the germinal centres of the follicles [18][19][20][21] where B lymphocytes acquire the ability to strongly express the cell surface antigen CD38 [22]. Subsequently, the primary B cell blasts of the germinal centre follow a differentiation pathway from centroblasts to centrocytes and then to either plasma cells or memory cells [23][24][25][26]. The ordered expression of sIgD, CD23 and CD38 allows B cells to be divided into subsets of different stages of maturation localized in follicular mantle and germinal centre compartments.…”

Section: Discussionmentioning

confidence: 99%

Age‐Associated Changes in the Cellular Composition of the Human Adenoid

Mattila

Tarkkanen

1997

Scand J Immunol

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Mattila PS, Tarkkanen J. Age-Associated Changes in the Cellular Composition of the Human Adenoid. Scand J Immunol 1997;45:423-427 Histological investigations suggest that the size and number of lymphoid follicles of the adenoids and tonsils decrease during ageing. The mechanisms underlying the histological changes are unknown. The authors have analysed the frequency of lymphocyte subpopulations in the adenoids by flow cytometry. The proportion of B lymphocytes decreased and the proportion of T lymphocytes of all mononuclear cells increased with age. Of all B lymphocytes the proportion of CD38 þ , surface IgD ¹ B lymphocytes representing the germinal centre cell phenotype, decreased and the proportion of CD38 ¹ , IgD ¹ B lymphocytes representing the mature B lymphocyte phenotype, increased with age. The expression of CD23, a cell surface molecule associated with activation of follicular mantle IgD þ B lymphocytes, did not change with increasing age. The results imply that the involution of the adenoid is associated with a decreased germinal centre reaction and relative accumulation of mature B cells in the adenoidal tissue, as analysed by three-colour flow cytometry.

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Section: Discussionmentioning

confidence: 99%

Age‐Associated Changes in the Cellular Composition of the Human Adenoid

Mattila

Tarkkanen

1997

Scand J Immunol

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“…Generation of antibody diversity is achieved mainly through evolutionarily determined germline repertoire, somatic rearrangement of germline V, D, and J genes to form a functional gene and somatic mutation. 13,14 Although the impact of V-D-J rearrangement and somatic hypermutation on antibody diversity has been studied extensively, [15][16][17][18][19] little is known about the contribution of genetic variation to antibody diversity. One of the genetic causes of antibody diversity is variation in gene number and composition due to the presence/absence of some genes in different haplotypes.…”

Section: Introductionmentioning

confidence: 99%

Determination of gene organization in the human IGHV region on single chromosomes

Pramanik

et al. 2005

Genes Immun

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Organization of the IGHV genes (n ¼ 108) on single human chromosomes has been determined by detecting these sequences in single sperm using multiplex PCR amplification followed by microarray detection. A total of 374 single sperm samples from five Caucasian males were studied. Three deletion/insertion polymorphisms (Del I-Del III) with deletion allele frequencies ranging from 0.1 to 0.3 were identified. Del I is a previously reported polymorphism affecting three IGHV genes (IGHV1-8, IGHV3-9, and IGHV2-10). Del II affects a region 2-18 kb containing two pseudogenes IGHV(II)-28.1 and IGHV3-29, and Del III spans B21-53 kb involving genes IGHV4-39, IGHV7-40, IGHV(II)-40-1, and IGHV3-41. Deletion alleles of both Dels II and III were found in a heterozygous state, and therefore, could not be easily detected if haploid samples were not used in the study. Results of the present study indicate that deletions/insertions together with other possible chromosomal rearrangements may play an important role in forming the genetic structure of the IGHV region, and may significantly contribute to antibody diversity. Since these three polymorphisms are located within or next to the 3 0 half of the IGHV region, they may have an important role in the expressed IGHV gene repertoire during immune response.

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“…It is known that GC reaction is primarily responsible for generation of memory B cells as well as the long-lived plasma cells (Berek et al, 1991;Gray, 1993;Jacob et al, 1991). Therefore, it is interesting that IgM-deficient mice exhibit vigorous GC formation during the primary response.…”

Section: Discussionmentioning

confidence: 99%

IgM-mediated signaling is required for the development of a normal B cell memory response

Guo

Zhang

Zheng

et al. 2008

Molecular Immunology

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Mature B cells co-express both IgM and IgD types of antigen receptors before activation. Our earlier work has shown that the co-expression of IgD and IgM plays an important role in regulating the composition of antibody repertoire during a primary immune response. However, the roles of these two B cell receptors in the development of B cell memory responses remain unclear. The present study shows that during the secondary immune response to (4-hydroxy-3-nitrophenyl)acetyl (NP), IgM -/-mice secreted significant amount of NP-specific IgD antibodies. The kinetics of antigenspecific IgD antibodies produced in IgM -/-mice was similar to that of IgM antibodies in wild type mice during the secondary response. However, the production of antigen specific class-switched antibodies in IgM -/-mice was significantly reduced compared to that in wild type mice, particularly at the early phase of the memory response. In addition, germinal center (GC) reaction was significantly diminished in IgM -/-mice after secondary challenge with soluble antigen. Nevertheless, affinity maturation of antibodies appears largely intact in IgM -/-mice during memory response. Thus, our studies demonstrate that IgM-mediated signaling plays an important role in the development of efficient B cell memory responses.

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Intraclonal generation of antibody mutants in germinal centres

Cited by 1,006 publications

References 22 publications

Age‐Associated Changes in the Cellular Composition of the Human Adenoid

Age‐Associated Changes in the Cellular Composition of the Human Adenoid

Determination of gene organization in the human IGHV region on single chromosomes

IgM-mediated signaling is required for the development of a normal B cell memory response

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