Truncation of the mu heavy chain alters BCR signalling and allows recruitment of CD5(+) B cells

Citation
Xg. Zou et al., Truncation of the mu heavy chain alters BCR signalling and allows recruitment of CD5(+) B cells, INT IMMUNOL, 13(12), 2001, pp. 1489-1499
Citations number
55
Categorie Soggetti
Immunology
Journal title
INTERNATIONAL IMMUNOLOGY
ISSN journal
09538178 → ACNP
Volume
13
Issue
12
Year of publication
2001
Pages
1489 - 1499
Database
ISI
SICI code
0953-8178(200112)13:12<1489:TOTMHC>2.0.ZU;2-O
Abstract
Ig are multifunctional molecules with distinct properties assigned to indiv idual domains. To assess the importance of IgM domain assembly in B cell de velopment we generated two transgenic mouse lines with truncated muH chains by homologous integration of the neomycin resistance gene (neo(r)) into ex ons C(mu)1 and C(mu)2. Upon DNA rearrangement shortened muH chain transcrip ts, V-H-D-J(H)-C(mu)3-C(mu)4, are produced independent of the transcription al orientation and termination signals provided by neo(r). The truncated mu H chain of similar to 52 kDa associates non-covalently with the L chain to form a monovalent HL heterodimer. Surface IgM is assembled into a defective BCR complex which has lost important signalling capacity. In immunizations with T-dependent and T-independent antigens, specific IgM antibodies canno t be detected, whilst IgG responses remain normal. B cell development in th e bone marrow is characterized by an increase in early B cells, but a decre ase of B220(+) cells from the stage when muH chain rearrangement is complet ed. The peritoneal lymphocyte population has elevated levels of CD5(+) B ce lls and their expansion may be the result of a negative feedback mechanism. The results show that antigenic stimulation is compromised by truncated mo novalent IgM and that this deficit in stimulation leads to reduced levels o f conventional B-2 lymphocytes, but dramatically increased levels of B-1 ce lls.