Affinity maturation in Lyn kinase-deficient mice with defective germinal center formation

Jun Kato, Noboru Motoyama, Ichiro Taniuchi, Hiromichi Takeshita, Masaki Toyoda, Keiji Masuda, Takeshi Watanabe

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42 Citations (Scopus)

Abstract

Lyn kinase-deficient (lyn(-/-)) mice show several abnormalities such as reduced numbers of circulating B cells, hyper-IgM, and low proliferative responses induced by CD40 ligand. Lyn(-/-) mice also develop splenomegaly, produce autoreactive Abs with age, and finally develop glomerulonephritis. Another abnormality observed in lyn(-/-) mice is that their disability to form germinal centers (GCs). It has been considered that GCs play an important role in affinity maturation and differentiation to B cell memory upon immunization with thymus-dependent Ag. Since Lyn kinase has been thought to be downstream of the signals from the B cell Ag receptor as well as CD40, we studied whether or not lyn(-/-) mice could exhibit normal Ag-specific class switching and affinity maturation following somatic hypermutation. The mice were immunized with (4-hydroxy-3-nitrophenyl) acetyl-chicken γ- globulin (NP-CG). Production of NP-specific IgG1 Abs was slightly reduced but clearly detectable. The affinity of Abs produced was comparable to that in wild-type mice. Furthermore, somatic hypermutation occurred in the heavy- chain variable region at the same level as that in wild-type mice. Therefore, we conclude that isotype switching and affinity maturation occur normally in lyn(-/-) mice without the formation of GCs. The results lead to a speculation that Lyn may not play a role in induction of isotype switching or affinity maturation, despite being downstream of the signals from the B cell Ag receptor complex and CD40, and that GC architecture may not be absolutely essential for affinity maturation.

Original languageEnglish
Pages (from-to)4788-4795
Number of pages8
JournalJournal of Immunology
Volume160
Issue number10
Publication statusPublished - May 15 1998

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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