The different process of class switching and somatic hypermutation; a novel analysis by CD27− naive B cells

Autor: Haruo Nagumo, Koji Shinozaki, Kozo Yasui, Masaya Takamoto, Kazunaga Agematsu, Norimoto Kobayashi, Kazuo Sugane, Hisashi Nagase, Sho Hokibara, Atsushi Komiyama
Rok vydání: 2002
Předmět:
Adult
Staphylococcus aureus
CD32
Transcription
Genetic
Cellular differentiation
Molecular Sequence Data
Plasma Cells
Immunology
Naive B cell
B-Lymphocyte Subsets
Immunoglobulin Variable Region
Receptors
Antigen
B-Cell
Somatic hypermutation
chemical and pharmacologic phenomena
Lymphocyte Activation
Transfection
Biochemistry
Humans
Amino Acid Sequence
CD40 Antigens
Gene Rearrangement
B-Lymphocyte
Blood Cells
CD40
Genes
Immunoglobulin
Sequence Homology
Amino Acid
biology
Receptors
IgG
Infant
Newborn
Antibodies
Monoclonal
Cell Differentiation
Cell Biology
Hematology
Cytidine deaminase
Fetal Blood
Immunoglobulin Class Switching
Molecular biology
Interleukin-10
Tumor Necrosis Factor Receptor Superfamily
Member 7
Immunoglobulin Isotypes
B-1 cell
Immunoglobulin class switching
Organ Specificity
Antibody Formation
biology.protein
Interleukin-2
Somatic Hypermutation
Immunoglobulin
Immunologic Memory
Sequence Alignment
Zdroj: Blood. 99:567-575
ISSN: 1528-0020
0006-4971
Popis: The relationship between class switch recombination (CSR) and somatic hypermutation has been unclear. By using human CD27− naive B cells, we investigated the somatic hypermutation and producibility of immunoglobulins (Igs) that occur after CSR. Although neither adult CD27− nor cord blood B cells, which showed the unmutated Ig V-region genes, produced IgG, IgM, or IgA in response to conventional stimuli, they produced IgG and IgM but not IgA in the presence of Staphylococcus aureus Cowan strain (SAC) + interleukin-2 (IL-2) + IL-10 + anti-CD40 mAb + CD32 transfectants (CD40/CD32T). The naive B cells also produced IgE when combined with IL-4 + CD40/CD32T. In parallel with IgG production, the expression of mature γ1 and γ 2 transcripts was induced from naive B cells by the stimuli. The CD27 expression on human naive B cells was induced remarkably by CD40 signaling or B-cell receptor engagement, but somatic hypermutation could not be induced. The proliferation and differentiation into plasma cells were induced from naive B cells, whereas most of the plasma cells displayed very low levels of mutations in Ig V-region genes. CD27− naive B cells expressed activation-induced cytidine deaminase messenger RNA by the stimuli later than CD27+memory B cells. Our results demonstrate that CSR, but not noticeable somatic hypermutation, can be induced from CD27− naive B cells upon B-cell receptor engagement and CD40 signaling in cooperation with cytokines, suggesting that CSR and somatic hypermutation processes can occur independently, and the antibodies produced in this in vitro system are low-affinity antibodies.
Databáze: OpenAIRE
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