TY - JOUR
T1 - T/B-cell interactions are more transient in response to weak stimuli in SLE-prone mice
AU - Sinai, Parisa
AU - Dozmorov, Igor M.
AU - Song, Ran
AU - Schwartzberg, Pamela L.
AU - Wakeland, Edward K.
AU - Wülfing, Christoph
N1 - Publisher Copyright:
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2014/12
Y1 - 2014/12
N2 - Changes in immune function during the course of systemic lupus erythematosus (SLE) are well characterized. Class-switched antinuclear antibodies are the hallmark of SLE, and T/B-cell interactions are thus critical. However, changes in immune function contributing to disease susceptibility are unknown. Here, we have analyzed primary T and B cells from a mouse model of SLE prior to the onset of disease. To allow cognate T-cell activation with low affinity, we have developed a lower potency peptide ligand for the OTII TCR. T- and B-cell couples formed less frequently and retained their polarity less efficiently preferentially in response to low-affinity stimulation in SLE-prone mice. This matched decreased recruitment of actin and Vav1 and an enhanced PKCΘ recruitment to the cellular interface in T cells. The induction of the GC B-cell marker GL7 was increased in T/B cell couples from SLE-prone mice when the T-cell numbers were limited. However, the overall gene expression changes were marginal. Taken together, the enhanced cellcouple transience may allow a more efficient sampling of a large number of T/B cell couples, preferentially in response to limiting stimuli, therefore enhancing the immune reactivity in the development of SLE.
AB - Changes in immune function during the course of systemic lupus erythematosus (SLE) are well characterized. Class-switched antinuclear antibodies are the hallmark of SLE, and T/B-cell interactions are thus critical. However, changes in immune function contributing to disease susceptibility are unknown. Here, we have analyzed primary T and B cells from a mouse model of SLE prior to the onset of disease. To allow cognate T-cell activation with low affinity, we have developed a lower potency peptide ligand for the OTII TCR. T- and B-cell couples formed less frequently and retained their polarity less efficiently preferentially in response to low-affinity stimulation in SLE-prone mice. This matched decreased recruitment of actin and Vav1 and an enhanced PKCΘ recruitment to the cellular interface in T cells. The induction of the GC B-cell marker GL7 was increased in T/B cell couples from SLE-prone mice when the T-cell numbers were limited. However, the overall gene expression changes were marginal. Taken together, the enhanced cellcouple transience may allow a more efficient sampling of a large number of T/B cell couples, preferentially in response to limiting stimuli, therefore enhancing the immune reactivity in the development of SLE.
KW - Actin
KW - Imaging
KW - Immunological synapse
KW - Protein kinase C
KW - Systemic lupus erythematosus
UR - http://www.scopus.com/inward/record.url?scp=84924302055&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924302055&partnerID=8YFLogxK
U2 - 10.1002/eji.201444602
DO - 10.1002/eji.201444602
M3 - Article
C2 - 25209945
AN - SCOPUS:84924302055
SN - 0014-2980
VL - 44
SP - 3522
EP - 3531
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -