Abstract
Mutations in the Bruton's tyrosine kinase (Btk) gene have been linked to severe early B cell developmental blocks in human X-linked agammaglobulinemia (XLA), and to milder B cell activation deficiencies in murine X-linked immune deficiency (Xid). To elucidate unequivocally potential Btk functions in mice, we generated mutations in embryonic stem cells, which eliminated the ability to encode Btk pleckstrin homology or kinase domains, and assayed their effects by RAG2-deficient blastocyst complementation or introduction into the germline. Both mutations block expression of Btk protein and lead to reduced numbers of mature conventional B cells, severe B1 cell deficiency, serum IgM and IgG3 deficiency, and defective responses in vitro to various B cell activators and in vivo to immunization with thymus-independent type II antigens. These results prove that lack of Btk function results in an Xid phenotype and further suggest a differential requirement for Btk during the early stages of murine versus human B lymphocyte development.
| Original language | English |
|---|---|
| Pages (from-to) | 283-299 |
| Number of pages | 17 |
| Journal | Immunity |
| Volume | 3 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 1 1995 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Infectious Diseases
Cite this
Defective B cell development and function in Btk-deficient mice. / Khan, Wasif; Alt, Frederick W.; Gerstein, Rachel M.; Malynn, Barbara A.; Larsson, Irene; Rathbun, Gary; Davidson, Laurie; Müller, Sussane; Kantor, Aaron B.; Herzenberg, Leonora A.; Rosen, Fred S.; Sideras, Paschalis.
In: Immunity, Vol. 3, No. 3, 01.01.1995, p. 283-299.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Defective B cell development and function in Btk-deficient mice
AU - Khan, Wasif
AU - Alt, Frederick W.
AU - Gerstein, Rachel M.
AU - Malynn, Barbara A.
AU - Larsson, Irene
AU - Rathbun, Gary
AU - Davidson, Laurie
AU - Müller, Sussane
AU - Kantor, Aaron B.
AU - Herzenberg, Leonora A.
AU - Rosen, Fred S.
AU - Sideras, Paschalis
PY - 1995/1/1
Y1 - 1995/1/1
N2 - Mutations in the Bruton's tyrosine kinase (Btk) gene have been linked to severe early B cell developmental blocks in human X-linked agammaglobulinemia (XLA), and to milder B cell activation deficiencies in murine X-linked immune deficiency (Xid). To elucidate unequivocally potential Btk functions in mice, we generated mutations in embryonic stem cells, which eliminated the ability to encode Btk pleckstrin homology or kinase domains, and assayed their effects by RAG2-deficient blastocyst complementation or introduction into the germline. Both mutations block expression of Btk protein and lead to reduced numbers of mature conventional B cells, severe B1 cell deficiency, serum IgM and IgG3 deficiency, and defective responses in vitro to various B cell activators and in vivo to immunization with thymus-independent type II antigens. These results prove that lack of Btk function results in an Xid phenotype and further suggest a differential requirement for Btk during the early stages of murine versus human B lymphocyte development.
AB - Mutations in the Bruton's tyrosine kinase (Btk) gene have been linked to severe early B cell developmental blocks in human X-linked agammaglobulinemia (XLA), and to milder B cell activation deficiencies in murine X-linked immune deficiency (Xid). To elucidate unequivocally potential Btk functions in mice, we generated mutations in embryonic stem cells, which eliminated the ability to encode Btk pleckstrin homology or kinase domains, and assayed their effects by RAG2-deficient blastocyst complementation or introduction into the germline. Both mutations block expression of Btk protein and lead to reduced numbers of mature conventional B cells, severe B1 cell deficiency, serum IgM and IgG3 deficiency, and defective responses in vitro to various B cell activators and in vivo to immunization with thymus-independent type II antigens. These results prove that lack of Btk function results in an Xid phenotype and further suggest a differential requirement for Btk during the early stages of murine versus human B lymphocyte development.
UR - http://www.scopus.com/inward/record.url?scp=0028847329&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028847329&partnerID=8YFLogxK
U2 - 10.1016/1074-7613(95)90114-0
DO - 10.1016/1074-7613(95)90114-0
M3 - Article
VL - 3
SP - 283
EP - 299
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -