Clonal selection and learning in the antibody system

  title={Clonal selection and learning in the antibody system},
  author={Klaus Rajewsky},
Each antibody-producing B cell makes antibodies of unique specificity, reflecting a series of ordered gene rearrangements which must be successfully performed if the cell is to survive. A second selection process occurs during immune responses in which a new antibody repertoire is generated through somatic hypermutation. Here only mutants binding antigen with high affinity survive to become memory cells. Cells expressing autoreactive receptors are counter-selected at both stages. This stringent… 
V(D)J recombination in mature B cells: a mechanism for altering antibody responses.
The ability to alter immunoglobulin expression by V(D)J recombination in the selective environment of the germinal center may be an additional mechanism for inactivation or diversification of immune responses.
Somatic Hypermutation and B-Cell Receptor Selection as Regulators of the Immune Response
  • C. Berek
  • Biology
    Transfusion Medicine and Hemotherapy
  • 2005
This work has shown that long lived memory and plasma cells are generated from a single antigen-activated B cell and this ensures the continued protection of the organism with high-affinity antibodies.
B-cell self-tolerance in humans.
Affinity maturation of the primary response by V gene diversification.
This chapter describes recent results from the laboratory and others which address the issue of affinity maturation of antibody-secreting cells in the primary response using the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled to a protein carrier as a model system.
B‐cell antigen receptor competence regulates B‐lymphocyte selection and survival
This work focuses here on studies indicating that the functional competence of the B-cell antigen receptor complex plays a central role in the fate of developing B cells and their antigen receptor genes.
Switched-memory B cells remodel B cell receptors within secondary germinal centers
It is demonstrated that vaccine boosts reactivate a cyclic program of GC function in class-switched memory B cells to remodel existing antibody specificities and enhance durable immunological protection.
Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells
It is shown that human memory B lymphocytes proliferate and differentiate into plasma cells in response to polyclonal stimuli, such as bystander T cell help and CpG DNA, which offers a means to maintain serological memory for a human lifetime.


Somatic generation of antibody diversity
In the genome of a germ-line cell, the genetic information for an immunoglobulin polypeptide chain is contained in multiple gene segments scattered along a chromosome which are assembled by recombination which leads to the formation of a complete gene.
Receptor editing in self-reactive bone marrow B cells
In mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors.
Development of the primary antibody repertoire.
The mechanism and control of these genomic rearrangement events and how aspects of this process are involved in generating the primary antibody repertoire are discussed.
Timing, Genetic Requirements and Functional Consequences of Somatic Hypermutation during B‐Cell Development
By constructing an antibody mutant through site-specific mutagenesis, it is shown that a point mutation in CDR1 of the heavy chain, found in most secondary anti-NP antibodies, is sufficient to increase NP binding affinity to the level typical for the secondary response.
Antigen-driven B cell differentiation in vivo
Data provide evidence for substantial proliferation within germinal centers before the initiation of somatic mutation and the subsequent selection of a significant frequency of mutated clonotypes into the memory compartment.
Stepwise intraclonal maturation of antibody affinity through somatic hypermutation.
  • C. Kocks, K. Rajewsky
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1988
Using recombinant DNA techniques, a genealogical tree is reconstructed that connects three clonally related B cells producing somatically mutated antibodies to a progenitor cell expressing a germ line-encoded antibody.
Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice
Findings indicate that self tolerance may result from mechanisms other than clonal deletion, and are consistent with the hypothesis that IgD may have a unique role in B-cell tolerance.
Generating the antibody repertoire in rabbit.