SOMATIC HYPERMUTATION OF IMMUNOGLOBULIN GENES

AN ANALYSIS OF THE SEQUENCES OF THE VARIABLE REGIONS OF BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS AND THEIR IMPLICATIONS FOR ANTIBODY COMPLEMENTARITY

1970 • 1,308 citations

The Specificity of Serological Reactions

1945 • 1,104 citations

Intraclonal generation of antibody mutants in germinal centres

1991 • 1,083 citations

Maturation of the immune response in germinal centers

1991 • 904 citations

Sites of specific B cell activation in primary and secondary responses to T cell‐dependent and T cell‐independent antigens

1991 • 743 citations

A hyperconversion mechanism generates the chicken light chain preimmune repertoire

1987 • 693 citations

A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks

1995 • 691 citations

Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections.

1993 • 691 citations

Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a γ2a variable region

1981 • 677 citations

Genes and Antibodies

1959 • 675 citations

Analysis of somatic mutation in five B cell subsets of human tonsil.

1994 • 667 citations

Mutation Drift and Repertoire Shift in the Maturation of the Immune Response

1987 • 635 citations

A complete immunoglobulin gene is created by somatic recombination.

1978 • 610 citations

Cell Selection by Antigen in the Immune Response

1969 • 594 citations

Generation of Memory B Cells and Plasma Cells in Vitro

1995 • 585 citations

Variability in the Lambda Light Chain Sequences of Mouse Antibody

1970 • 554 citations

Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin.

1984 • 545 citations

Somatic mutation and the maturation of immune response to 2-phenyl oxazolone

1984 • 534 citations

IgG antibodies to phosphorylcholine exhibit more diversity than their IgM counterparts

1981 • 509 citations

Sequences of mouse immunoglobulin light chain genes before and after somatic changes

1978 • 495 citations

The Specificity of Serological Reactions

1945 • 484 citations

Somatic hyperconversion diversifies the single VH gene of the chicken with a high incidence in the D region

1989 • 467 citations

Somatic hypermutagenesis in immunoglobulin genes

1992 • 458 citations

Amino acid sequence studies with Bence-Jones proteins.

1965 • 385 citations

Elements regulating somatic hypermutation of an immunoglobulin κ gene: Critical role for the intron enhancer/matrix attachment region

1994 • 382 citations

In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells.

1993 • 367 citations

A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION

1935 • 349 citations

Antibody diversity: Somatic hypermutation of rearranged VH genes

1981 • 334 citations

Boundaries of somatic mutation in rearranged immunoglobulin genes: 5' boundary is near the promoter, and 3' boundary is approximately 1 kb from V(D)J gene.

1990 • 318 citations

Hypermutation generating the sheep immunoglobulin repertoire is an antigen-independent process

1995 • 318 citations

Analysis of the repertoire of anti‐NP antibodies in C57BL/6 mice by cell fusion. I. Characterization of antibody families in the primary and hyperimmune response

1978 • 316 citations

Origin of Antibody Variation

1966 • 314 citations

mRNA sequences define an unusually restricted IgG response to 2-phenyloxazolone and its early diversification

1983 • 301 citations

Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation

1993 • 283 citations

Antibody engineering for the analysis of affinity maturation of an anti-hapten response.

1988 • 275 citations

Kinetic maturation of an immune response

1991 • 274 citations

Passenger transgenes reveal intrinsic specificity of the antibody hypermutation mechanism: clustering, polarity, and specific hot spots.

1993 • 271 citations

Clusters of point mutations are found exclusively around rearranged antibody variable genes.

1983 • 233 citations

Targeting of non-lg sequences in place of the V segment by somatic hyper mutation

1995 • 223 citations

Linked Groups of Residues in Immunoglobulin κ Chains

1967 • 216 citations

Somatic evolution of variable region structures during an immune response.

1986 • 211 citations

Rearrangement of genetic information may produce immunoglobulin diversity

1978 • 209 citations

Somatic mutation of immunoglobulin light-chain variable-region genes

1981 • 184 citations

What limits affinity maturation of antibodies in Xenopus--the rate of somatic mutation or the ability to select mutants?

1992 • 179 citations

Structural Studies of Immunoglobulins

1973 • 179 citations

Human IgM⁺IgD⁺ B cells, the major B cell subset in the peripheral blood, express Vϰ genes with no or little somatic mutation throughout life

1993 • 166 citations

Differences between germ-line and rearranged immunoglobulin Vκ coding sequences suggest a localized mutation mechanism

1981 • 161 citations

Patterns of Somatic Mutations in Immunoglobulin Variable Genes

1987 • 158 citations

Somatic mutation and clonal expansion of B cells in an antigen-driven immune response.

1985 • 153 citations

Antibody diversity in lower vertebrates—why is it so restricted?

1982 • 151 citations

Hypermutation at the immunoglobulin heavy chain locus in a pre-B-cell line.

1985 • 150 citations

Where transcription meets repair

1994 • 148 citations

Rates of Transition and Transversion in Coding Sequences since the Human-Rodent Divergence

1994 • 147 citations

Experimental analysis by site-directed mutagenesis of somatic mutation effects on affinity and fine specificity in antibodies specific for lysozyme.

1992 • 146 citations

Rabbit IgH sequences in appendix germinal centers: VH diversification by gene conversion-like and hypermutation mechanisms

1994 • 144 citations

Locus-specific somatic hypermutation in germinal centre T cells

1994 • 134 citations

Somatic hypermutation of immunoglobulin kappa may depend on sequences 3′ of C kappa and occurs on passenger transgenes.

1991 • 132 citations

Expressed human immunoglobulin ϰ genes and their hypermutation

1993 • 130 citations

Distribution of Mutations around Rearranged Heavy-Chain Antibody Variable-Region Genes

1990 • 129 citations

The Contribution of Contact and Non-contact Residues of Antibody in the Affinity of Binding to Antigen

1993 • 128 citations

Somatic variation precedes extensive diversification of germline sequences and combinatorial joining in the evolution of immunoglobulin heavy chain diversity.

1993 • 128 citations

SEQUENTIAL CHANGES IN THE RELATIVE AFFINITY OF ANTIBODIES SYNTHESIZED DURING THE IMMUNE RESPONSE

1967 • 122 citations

Anti-oxazolone hybridomas and the structure of the oxazolone idiotype.

1983 • 114 citations

Somatic hypermutation of an immunoglobulin transgene in K transgenic mice

1987 • 110 citations

Variable region gene analysis of B cell subsets derived from a 4-year-old child: somatically mutated memory B cells accumulate in the peripheral blood already at young age.

1994 • 108 citations

Analysis of somatic hypermutation in mouse Peyer's patches using immunoglobulin kappa light-chain transgenes.

1993 • 108 citations

Repair and Transcription: Collision or collusion?

1994 • 97 citations

Somatic diversification of immunoglobulins.

1984 • 94 citations

Might gene conversion be the mechanism of somatic hypermutation of mammalian immunoglobulin genes?

1989 • 94 citations

GENE CONVERSION AND THE GENERATION OF ANTIBODY DIVERSITY

1989 • 93 citations

Multiplicity of germline genes specifying a group of related mouse κ chains with implications for the generation of immunoglobulin diversity

1978 • 93 citations

Distribution of mutations around rearranged heavy-chain antibody variable-region genes.

1990 • 93 citations

The Maintenance and Regulation of Serum Antibody Levels: Evidence Indicating a Role for Antigen Retained in Lymphoid Follicles

1978 • 87 citations

The 5′ boundary of somatic hypermutation in a Vχ gene is in the leader intron

1994 • 86 citations

Mutational hot spots in Ig V region genes of human follicular lymphomas.

1988 • 86 citations

Development of antibody diversity in single germinal centers: selective expansion of high‐affinity variants

1994 • 85 citations

Mutations of the chloramphenicol acetyl transferase transgene driven by the immunoglobulin promoter and intron enhancer

1993 • 77 citations

Human immunoglobulin transgenes undergo rearrangement, somatic mutation and class switching in mice that lack endogenous IgM

1994 • 74 citations

Evolution of antibody structure during the immune response. The differentiative potential of a single B lymphocyte.

1989 • 71 citations

Somatic hypermutation in 5′ flanking regions of heavy chain antibody variable regions

1993 • 69 citations

Lack of heterogeneity in anti-hapten antibodies of a phylogenetically primitive shark

1980 • 69 citations

Mutation pattern of immunoglobulin transgenes is compatible with a model of somatic hypermutation in which targeting of the mutator is linked to the direction of DNA replication.

1991 • 69 citations

Somatic hypermutation of an immunoglobulin mu heavy chain transgene.

1993 • 69 citations

Somatic mutation of immunoglobulin lambda chains: a segment of the major intron hypermutates as much as the complementarity-determining regions.

1994 • 69 citations

Mapping the upstream boundary of somatic mutations in rearranged immunoglobulin transgenes and endogenous genes

1994 • 69 citations

Point mutations cause the somatic diversification of IgM and IgG2a antiphosphorylcholine antibodies.

1988 • 66 citations

Generation of immunoglobulin light chain gene diversity in Raja erinacea is not associated with somatic rearrangement, an exception to a central paradigm of B cell immunity.

1995 • 66 citations

V gene rearrangement is required to fully activate the hypermutation mechanism in B cells.

1989 • 64 citations

Heavy chain variable region. Multiple gene segments encode anti-4-(hydroxy-3-nitro-phenyl)acetyl idiotypic antibodies.

1985 • 63 citations

Hypermutation is observed only in antibody H chain V region transgenes that have recombined with endogenous immunoglobulin H DNA: implications for the location of cis-acting elements required for somatic mutation.

1993 • 62 citations

Genetic basis of the antibody repertoire in Xenopus: analysis of the Vh diversity.

1989 • 62 citations

Defining subsets of naive and memory B cells based on the ability of their progeny to somatically mutate in vitro

1995 • 55 citations

The BALB/c secondary response to the Sb site of influenza virus hemagglutinin. Nonrandom silent mutation and unequal numbers of VH and Vk mutations.

1990 • 55 citations

Somatic mutation in constant regions of mouse lambda 1 light chains.

1991 • 55 citations

The efficiency of antibody affinity maturation: can the rate of B-cell division be limiting?

1990 • 54 citations

Analysis of Sequence Transfers Resembling Gene Conversion in a Mouse Antibody Transgene

1994 • 46 citations

The diversity of antigen‐specific monoclonal antibodies from transgenic mice bearing human immunoglobulin gene miniloci

1994 • 44 citations

Somatic diversification is required to generate the V kappa genes of MOPC 511 and MOPC 167 myeloma proteins.

1981 • 42 citations

Age‐related decrease in the proportion of germinal center B cells from mouse Peyer's patches is accompanied by an accumulation of somatic mutations in their immunoglobulin genes

1994 • 41 citations

Somatic point mutations in unrearranged immunoglobulin gene segments encoding the variable region of lambda light chains.

1987 • 40 citations

Mutation in a reporter gene depends on proximity to and transcription of immunoglobulin variable transgenes.

1991 • 39 citations

Lack of somatic mutation in a χ light chain transgene

1990 • 38 citations

Immunoglobulin variable region hypermutation in hybrids derived from a pre-B- and a myeloma cell line.

1995 • 37 citations

DNA sequence of the constant gene region of the mouse immunoglobulin kappa chain

1981 • 36 citations

Bias in somatic hypermutation of human V_H genes

1994 • 35 citations

Pecularities of immunoglobulin gene structures as a basis for somatic mutation emergence

1987 • 35 citations

Analysis of a T cell receptor gene as a target of the somatic hypermutation mechanism.

1992 • 34 citations

Somatically mutated forms of a major anti-p-azophenylarsonate antibody variable region with drastically reduced affinity for p-azophenylarsonate. By-products of an antigen-driven immune response?

1987 • 31 citations

Germ line variable regions that match hypermutated sequences in genes encoding murine anti-hapten antibodies.

1992 • 28 citations

A λ1 transgene under the control of a heavy chain promoter and enhancer does not undergo somatic hypermutation

1994 • 27 citations

Maturation of the humoral immune response as an optimization problem

1991 • 21 citations

Diversity and the genesis of high affinity antibodies

1987 • 13 citations

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