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

Research output: Contribution to journalArticle

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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

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Germinal Center
Phosphotransferases
Immunoglobulin Class Switching
B-Lymphocytes
CD40 Ligand
Splenomegaly
Globulins
Glomerulonephritis
Thymus Gland
Immunoglobulin M
Chickens
Immunization
Immunoglobulin G

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kato, J., Motoyama, N., Taniuchi, I., Takeshita, H., Toyoda, M., Masuda, K., & Watanabe, T. (1998). Affinity maturation in Lyn kinase-deficient mice with defective germinal center formation. Journal of Immunology, 160(10), 4788-4795.

Affinity maturation in Lyn kinase-deficient mice with defective germinal center formation. / Kato, Jun; Motoyama, Noboru; Taniuchi, Ichiro; Takeshita, Hiromichi; Toyoda, Masaki; Masuda, Keiji; Watanabe, Takeshi.

In: Journal of Immunology, Vol. 160, No. 10, 15.05.1998, p. 4788-4795.

Research output: Contribution to journalArticle

Kato, J, Motoyama, N, Taniuchi, I, Takeshita, H, Toyoda, M, Masuda, K & Watanabe, T 1998, 'Affinity maturation in Lyn kinase-deficient mice with defective germinal center formation', Journal of Immunology, vol. 160, no. 10, pp. 4788-4795.
Kato J, Motoyama N, Taniuchi I, Takeshita H, Toyoda M, Masuda K et al. Affinity maturation in Lyn kinase-deficient mice with defective germinal center formation. Journal of Immunology. 1998 May 15;160(10):4788-4795.
Kato, Jun ; Motoyama, Noboru ; Taniuchi, Ichiro ; Takeshita, Hiromichi ; Toyoda, Masaki ; Masuda, Keiji ; Watanabe, Takeshi. / Affinity maturation in Lyn kinase-deficient mice with defective germinal center formation. In: Journal of Immunology. 1998 ; Vol. 160, No. 10. pp. 4788-4795.
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