Somatic diversification of the B cell repertoire requires two cell subsets. 2018

M Cohn
Conceptual Immunology Group, The Salk Institute, La Jolla, CA, USA.

Evolution found itself in a Catch-22 situation when selecting for the somatically derived paratopic repertoire of the humoral immune system. The B cell BCR repertoire can only be somatically diversified from a substrate of paratopes that is encoded in the germline. In order for the cells expressing that substrate to also be a target of germline selection, their BCRs must, independently, be of selective value by being expressed in a functionally important way in each individual. A somatically derived repertoire scrambles this substrate so that its specificities are lost, making it unselectable in the germline. Consequently, evolution faced an incompatibility. Here, we explore what it takes to resolve it.

UI MeSH Term Description Entries
D007135 Immunoglobulin Variable Region That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions. Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D005803 Genes, Immunoglobulin Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity). Genes, Ig,Immunoglobulin Genes,Gene, Ig,Gene, Immunoglobulin,Ig Gene,Ig Genes,Immunoglobulin Gene
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000906 Antibodies Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
D001666 Binding Sites, Antibody Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS. Antibody Binding Sites,Paratopes,Antibody Binding Site,Binding Site, Antibody,Paratope
D016175 B-Lymphocyte Subsets A classification of B-lymphocytes based on structurally or functionally different populations of cells. B-Cell Subsets,Tumor-Infiltrating B Cells,Tumor-Infiltrating B Lymphocytes,B Effector 1 Cells,B Effector 2 Cells,B-1 Cells,B-1 Lymphocytes,B-2 Lymphocytes,B-Lymphocytes, Effector,B1 Lymphocytes,B2 Lymphocytes,Be1 Cells,Be2 Cells,Effector B Cells,B 1 Cells,B 1 Lymphocytes,B 2 Lymphocytes,B Cell Subsets,B Cell, Tumor-Infiltrating,B Lymphocyte Subsets,B Lymphocyte, Tumor-Infiltrating,B-1 Cell,B-1 Lymphocyte,B-2 Lymphocyte,B-Cell Subset,B-Lymphocyte Subset,B-Lymphocyte, Effector,B1 Lymphocyte,B2 Lymphocyte,Be1 Cell,Be2 Cell,Cell, B-1,Cell, Be1,Cell, Be2,Effector B Cell,Effector B-Lymphocyte,Effector B-Lymphocytes,Lymphocyte, B-1,Lymphocyte, B-2,Lymphocyte, B1,Lymphocyte, B2,Tumor Infiltrating B Cells,Tumor Infiltrating B Lymphocytes,Tumor-Infiltrating B Cell,Tumor-Infiltrating B Lymphocyte
D056724 Immunity, Humoral Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION. Humoral Immune Response,Humoral Immune Responses,Humoral Immunity,Immune Response, Humoral,Immune Responses, Humoral,Response, Humoral Immune
D061905 Single-Domain Antibodies An immunoglobulin fragment composed of one variable domain from an IMMUNOGLOBULIN HEAVY CHAIN or IMMUNOGLOBULIN LIGHT CHAIN. Single-Domain Antibody,VHH Antibodies,VHH Antibody,Immunoglobulin VH Domain Fragments,Immunoglobulin VL Domain Fragments,Nanobodies,VH Domain Fragments,VHH Fragments,VHH Immunoglobulin Fragments,VL Domain Fragments,VNAR Fragments,VNAR Immunoglobulin Fragments,Antibody, Single-Domain,Antibody, VHH,Single Domain Antibody
D019070 Cell Lineage The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo. Cell Lineages,Lineage, Cell,Lineages, Cell

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