TY - JOUR
T1 - AID-/-μs-/- mice are agammaglobulinemic and fail to maintain B220-CD138+ plasma cells
AU - Kumazaki, Kaori
AU - Tirosh, Boaz
AU - Maehr, René
AU - Boes, Marianne
AU - Honjo, Tasuku
AU - Ploegh, Hidde L.
PY - 2007/2/15
Y1 - 2007/2/15
N2 - The terminal stage of B cell differentiation culminates in the formation of plasma cells (PC), which secrete large quantities of Igs. Despite recent progress in understanding the molecular aspect of PC differentiation and maintenance, the requirement for the synthesis of secretory Igs as a contributing factor has not been explored. To address this issue, we generated activation-induced cytidine deaminase (AID)/secretory μ-chain (μs) double-knockout mice, in which a normally diverse repertoire of B cell receptors is retained, yet B cells are unable to synthesize secretory Igs. These mice possess polyclonal B cells but have no serum Igs. Following immunization to vivo, PCs, identified by CD138 expression and loss of the B220 marker, were starkly reduced in number in spleen and bone marrow of AID -/-μ-/- agammaglobulinemic mice compared with wild-type mice. Upon mitogenic stimulation in vitro, AID-/-μ-/- B cells differentiated into plasmablasts to some extent, but showed reduced survival compared with wild-type B cells. We found no evidence that this reduced survival was attributable to accumulation of membrane IgM. Our results indicate that the synthesis of secretory Igs is a requirement for maintenance of B220-CD138+ PCs.
AB - The terminal stage of B cell differentiation culminates in the formation of plasma cells (PC), which secrete large quantities of Igs. Despite recent progress in understanding the molecular aspect of PC differentiation and maintenance, the requirement for the synthesis of secretory Igs as a contributing factor has not been explored. To address this issue, we generated activation-induced cytidine deaminase (AID)/secretory μ-chain (μs) double-knockout mice, in which a normally diverse repertoire of B cell receptors is retained, yet B cells are unable to synthesize secretory Igs. These mice possess polyclonal B cells but have no serum Igs. Following immunization to vivo, PCs, identified by CD138 expression and loss of the B220 marker, were starkly reduced in number in spleen and bone marrow of AID -/-μ-/- agammaglobulinemic mice compared with wild-type mice. Upon mitogenic stimulation in vitro, AID-/-μ-/- B cells differentiated into plasmablasts to some extent, but showed reduced survival compared with wild-type B cells. We found no evidence that this reduced survival was attributable to accumulation of membrane IgM. Our results indicate that the synthesis of secretory Igs is a requirement for maintenance of B220-CD138+ PCs.
UR - http://www.scopus.com/inward/record.url?scp=33846919353&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.178.4.2192
DO - 10.4049/jimmunol.178.4.2192
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C2 - 17277124
AN - SCOPUS:33846919353
SN - 0022-1767
VL - 178
SP - 2192
EP - 2203
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -