AFFINITY MATURATION IN LYN KINASE-DEFICIENT MICE WITH DEFECTIVE GERMINAL CENTER FORMATION

Lyn kinase-deficient (lyn(-/-)) mice show several abnormalities such a s reduced numbers of circulating B cells, hyper-IgM, and low prolifera tive responses induced by CD40 ligand, Lyn(-/-) mice also develop sple nomegaly, produce autoreactive Abs with age, and finally develop glome rulonephritis. Another abnormality observed in lyn(-/-) mice is that t heir disability to form germinal centers (GCs). It has been considered that GCs play an important role in affinity maturation and differenti ation to B cell memory upon immunization with thymus dependent Ag, Sin ce Lyn kinase has been thought to be downstream of the signals from th e 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 wi th (4-hydroxy-3-nitrophenyl)acetyl-chicken gamma-globulin (NP-CG). Pro duction of NP-specific IgG1 Abs was slightly reduced but clearly detec table, The affinity of Abs produced was comparable to that in wild-typ e mice, Furthermore, somatic hypermutation occurred in the heavy-chain variable region at the same level as that in wild-type mice. Therefor e, we conclude that isotype switching and affinity maturation occur no rmally 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 sig nals from the B cell Ag receptor complex and CD40, and that GC archite cture may not be absolutely essential for affinity maturation.