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
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.