The different process of class switching and somatic hypermutation; a novel analysis by CD27(-) naive B cells.
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 gamma1 and gamma 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.
Nagumo
Haruo
H
Shinshu University, Graduate School of Medicine, Department of Infectious Immunology and Pediatrics, Matsumoto, Japan.
Agematsu
Kazunaga
K
Kobayashi
Norimoto
N
Shinozaki
Koji
K
Hokibara
Sho
S
Nagase
Hisashi
H
Takamoto
Masaya
M
Yasui
Kozo
K
Sugane
Kazuo
K
Komiyama
Atsushi
A
D000328:Adult; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000917:Antibody Formation; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D001773:Blood Cells / Q000166:cytology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D005312:Fetal Blood / Q000166:cytology; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010950:Plasma Cells / Q000166:cytology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D027041:Somatic Hypermutation, Immunoglobulin; D013211:Staphylococcus aureus / Q000276:immunology; D014158:Transcription, Genetic; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis / Q000502:physiology*
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region; D007376:Interleukin-2; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10