Abstract
We have studied the induction and maintenance of tolerance in the B lymphocyte compartment. Neonatal and adult transgenic mice which expressed either surface IgM (sIgM) or sIgM and sIgD anti-2,4,6-trinitrophenyl (TNP) were treated with soluble mono- and multivalent forms of TNP-modified carriers. We compared the B cell compartment of mice treated with antigen and of littermates injected with phosphate-buffered saline. Antigen-mediated cross-linking of membrane-bound IgM (sIgM) caused deletion of B cells both in neonatal and adult mice with μ and κ transgenes. Deletion was the result of apoptosis. In mice that carried an additional δ transgene sIgD interfered with tolerance induction. The stage in which the cells were sensitive to deletion was characterized as a transitional stage between immature (sIgM(dull), heat-stable antigen(bright), B220(dull), sIgD-) and more mature (IgM(bright), heat-stable antigen(dull), B22O(bright), sIgD-) B cells. Surviving cells were functional as measured by receptor-mediated changes in the intracellular free Ca2+ concentration. We propose that when the immature B cells have reached the final stages of maturation IgM always transmits negative signals in the absence of T cell help. When B cells need to be screened against self reactivity IgM is the only antigen receptor expressed. The presence of sIgD protects resting B cells from deletion and allows them to initiate an effective immune response.
| Original language | English |
|---|---|
| Pages (from-to) | 168-178 |
| Number of pages | 11 |
| Journal | European Journal of Immunology |
| Volume | 23 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1993 |
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Keywords
- B cell development
- IgD
- IgM
- Tolerance
- Transgenic mice
ASJC Scopus subject areas
- Immunology
Cite this
A role for immunoglobulin D : Interference with tolerance induction. / Carsetti, R.; Kohler, G.; Lamers, M. C.
In: European Journal of Immunology, Vol. 23, No. 1, 1993, p. 168-178.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A role for immunoglobulin D
T2 - Interference with tolerance induction
AU - Carsetti, R.
AU - Kohler, G.
AU - Lamers, M. C.
PY - 1993
Y1 - 1993
N2 - We have studied the induction and maintenance of tolerance in the B lymphocyte compartment. Neonatal and adult transgenic mice which expressed either surface IgM (sIgM) or sIgM and sIgD anti-2,4,6-trinitrophenyl (TNP) were treated with soluble mono- and multivalent forms of TNP-modified carriers. We compared the B cell compartment of mice treated with antigen and of littermates injected with phosphate-buffered saline. Antigen-mediated cross-linking of membrane-bound IgM (sIgM) caused deletion of B cells both in neonatal and adult mice with μ and κ transgenes. Deletion was the result of apoptosis. In mice that carried an additional δ transgene sIgD interfered with tolerance induction. The stage in which the cells were sensitive to deletion was characterized as a transitional stage between immature (sIgM(dull), heat-stable antigen(bright), B220(dull), sIgD-) and more mature (IgM(bright), heat-stable antigen(dull), B22O(bright), sIgD-) B cells. Surviving cells were functional as measured by receptor-mediated changes in the intracellular free Ca2+ concentration. We propose that when the immature B cells have reached the final stages of maturation IgM always transmits negative signals in the absence of T cell help. When B cells need to be screened against self reactivity IgM is the only antigen receptor expressed. The presence of sIgD protects resting B cells from deletion and allows them to initiate an effective immune response.
AB - We have studied the induction and maintenance of tolerance in the B lymphocyte compartment. Neonatal and adult transgenic mice which expressed either surface IgM (sIgM) or sIgM and sIgD anti-2,4,6-trinitrophenyl (TNP) were treated with soluble mono- and multivalent forms of TNP-modified carriers. We compared the B cell compartment of mice treated with antigen and of littermates injected with phosphate-buffered saline. Antigen-mediated cross-linking of membrane-bound IgM (sIgM) caused deletion of B cells both in neonatal and adult mice with μ and κ transgenes. Deletion was the result of apoptosis. In mice that carried an additional δ transgene sIgD interfered with tolerance induction. The stage in which the cells were sensitive to deletion was characterized as a transitional stage between immature (sIgM(dull), heat-stable antigen(bright), B220(dull), sIgD-) and more mature (IgM(bright), heat-stable antigen(dull), B22O(bright), sIgD-) B cells. Surviving cells were functional as measured by receptor-mediated changes in the intracellular free Ca2+ concentration. We propose that when the immature B cells have reached the final stages of maturation IgM always transmits negative signals in the absence of T cell help. When B cells need to be screened against self reactivity IgM is the only antigen receptor expressed. The presence of sIgD protects resting B cells from deletion and allows them to initiate an effective immune response.
KW - B cell development
KW - IgD
KW - IgM
KW - Tolerance
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=0027389198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027389198&partnerID=8YFLogxK
U2 - 10.1002/eji.1830230127
DO - 10.1002/eji.1830230127
M3 - Article
C2 - 8419167
AN - SCOPUS:0027389198
VL - 23
SP - 168
EP - 178
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 1
ER -