??af??e?a 1

1
?????? ??S ??F??S?S ?O? TNFRSF13B/TACI ???
TNFRSF13C/BAFFR S? ?ST????S ?? ?????? ?
???F????????S???? S???????
?. ?aµ??a 1, F. ?pa?d??a 1, ?. ?a?da?? 2, ?.
?a?as?p????? 3, ?. ???ts??? 4, ?. ??ad??? 1, ?.
G?a??a????a? 3, ?. ?s???? 2, S.?f?a?µ?d??4, ?.
?apad????? 5, ?. ?a?t?s?? 6, ?. ?ats???? 2, F.
?a?a?? 1, ?. Spe??ta? 1 1???ast????
???s?????a?-?st?s?µßat?t?ta?, ?a?ep?st?µ?a??
??s???µe?? ????sa?, 2? ?a?ep?st?µ?a?? ?a????????
???????, ?pp????te?? ??s???µe?? Tessa???????,
3??µat??????? ???????, ?a?ep?st?µ?a?? ??s???µe??
????sa?, 4??µat??????? ?µ?µa, ??s???µe??
?apa?e?????? Tessa???????, 5??µat??????? ?µ?µa,
Ge???? ??s???µe?? ????sa?, 6??µat??????? ?µ?µa,
Ge???? ??s???µe?? ?a???da?
??S?GOG?
????? ??? ??T????
?? ?p?d??e?? TNFRSF13B/TACI ?a? TNFRSF13C/BAFFR
ep????? µ???p?t?a e?e???p???s?? t?? µeta??af????
pa?????ta NF-?? ?a? pa????? s?µa?t??? ???? st??
?µ???stas?, t?? ?s?t?p??? µetast??f? ?a? t?
d?af???p???s? t?? f?s????????? ?eµf???tt????.
???sfate? µe??te? ????? de??e? ?t? ?e?p?asµat???
??tta?a as?e??? µe ? ?????a ?eµf??pe?p?ast???
s??d??µa (?-??S) e?f?????? µe µe???? p??????a
t??? ?p?d??e?? a?t???, µe ????st? µ???? s?µe?a
ß???????? s?µas?a. S??p?? t?? pa???sa? µe??t??
?ta? ? a????s? t?? ??f?as?? t?? pa?ap???
?p?d????? se as?e?e?? µe ?-??S ?a? ? a??de??? t??
p??a??? ???????? t??? s?µas?a?.
?e?et????a? 123 as?e?e?? (?/G 73/50, µ?s?
?????a 67.2 ?t?, e???? 34-91) µe ??S (91 µe
?-?????a ?eµf???tta???? ?e??a?µ?a ?-??? ?a? 32
µe Non-Hodgkin ?eµf?µata NHL ?aµ???? ßa?µ??
?a????e?a?) ?a? 157 f?s????????? µ??t??e? (?/G
90/67, µ?s? ?????a 67.9 ?t?, e???? 21-90). Se
??a ta de??µata p?a?µat?p??????e ????????µ????
a?µat????????, a??s?fa???t?p???? ?a? ??????????
??e????, e?? st??? as?e?e?? µe ?-??S ????e
?ata??af? t?? a?t????s?? e?d???se??, ?a??? ?a?
t?? s????t?ta? ?a? e?t?p?s?? t?? ???µ??e??. St???
as?e?e?? µe B-??? µe?et????e ep?s?? ? ??f?as? t??
µ????? CD38 ?a? Zap-70 µe ??tta??µet??a ????,
?a??? ?a? ?? ?pe?µeta????e?? t?? ßa???? a??s?da?
t?? a??s?sfa?????? µe PCR-sequencing. ?
p??te????? ??f?as? t?? ?p?d????? TACI ?a? BAFFR
e???????e µe ??tta??µet??a ???? (?????? 1a1/Abcam
?a? 11C1/Biolegend, a?t?st???a), e?? ? µ???a??
??f?as? t?? TNFRSF13B/TACI ?a? TNFRSF13C/BAFFR µe
Q-RT-PCR.

???????S????
??a ta ?e?p?asµat??? ??tta?a as?e??? µe ?-??S
e??f?a?a? p??t?te BAFFR, a??? µe s?µa?t???
?aµ???te?? ??tas? f????sµ?? s?????t??? µe ta
f?s???????? ? ??tta?a (µ?s? t?µ?SD 6.73.1 vs
10.75.9, plt0.001). ?a???s???eta? e?de??t??? ?
pe??pt?s? as?e???? µe ?-??? p?? d???ete ??a?
f?s???????? p????sµ? ? ?eµf???tt???? ? ?p????
e??f?a?e BAFFR µe µe???? ??tas? f????sµ?? ?a?
??a? pa???????? p????sµ? µe ??f?as? BAFFR ?aµ????
??tas?? f????sµ?? (???. 1).
H p?e????t?ta t?? as?e??? µe B-???
pa???s?a?e p??? ?aµ??? ??f?as? TACI (µ?s?
t?µ?SD 13.422.0), se s??s? t?s? µe t???
f?s?????????? µ??t??e? (26.314.0), ?s? ?a? t???
as?e?e?? µe NHL (36.829.0) (plt0.001 ?a? st?? d??
pe??pt?se??) (???. 2 ?a? 3).
?????a 1 ??f?as? BAFFR sta f?s???????? ?a?
?e?p?asµat??? ? ?eµf???tta?a as?e???? µe ?-???
?a e???µata t?? p??te?????? ??f?as?? t??
?p?d????? ep?ßeßa?????a? ?a? se µeta??af???
ep?ped?. Ost?s?, de? d?ap?st????e s?s??t?s? t??
??f?as?? t?? ?p?d????? TACI ?a? BAFFR µe t??
pa???s?a a?t????s?? e?d???se??, ???µ??e??, ? t??
??f?as? ???st?? p?????st???? de??t?? t?? ?-???.
?a???? p?? ? p?e????t?ta t?? as?e??? µe B-???
pa???s?a?e p??? ?aµ??? ??f?as? TAC?, ?p???a? ?a?
pe??pt?se?? µ?s?? ? ?????? ??f?as??.
?p?p??s?eta, ? ?a??????e?a ?-??? ??tt???? ??????
?a? ?aµ???? ??f?as?? TACI, pa???s?a t?? p??sdet??
BAFF ?a? ?PRIL ?atade????e? t?? ??a??t?ta t??
TACI ?a p??state?e? ta ?e?p?asµat??? ?
?eµf???tta?a ap? t?? ap?pt?s?.
?????a 2 ??f?as? TACI se as?e?? µe ?-??? ?a? se
f?s???????? µ??t??a
S?µpe??sµata ? ?aµ??? ??f?as? TACI ap?te?e?
?a?a?t???st??? e???µa ??a t?? p?e????t?ta t??
as?e??? µe ?-??? ?a? s?et??eta? µe t?? epa????
t?? ap?pt?s?? ????? ?a ep??e??e? t?? ß????????
p??e?a t?? ??s??. ?p? t?? ????, t? p??t?p?
??f?as?? t?? BAFFR ap? ta ?e?p?asµat??? ?
?eµf???tta?a µp??e? ?a t? ?atast?se? afe??? ??a
???s?µ? de??t? ??a t?? ??e??? t?? ?p??e?p?µe???
??s??, a??? ?a? st??? ep??e?µ???? ?e?ape?t????
pa?eµß?se??.
?????a 3 ??s? ??f?as? TACI se as?e?e?? µe ?-??S
?a? f?s?????????? µ??t??e?
??ß?????af?a 1. Novak AJ, et al. Aberrant
expression of B-lymphocyte stimulator by B
chronic lymphocytic leukemia cells a mechanism
for survival. Blood 2002, Oct 15100(8)2973-9 2.
Kern C, et al. Involvement of BAFF and APRIL in
the resistance to apoptosis of B-CLL through an
autocrine pathway. Blood 2004103679-88 3. Novak
AJ, et al. Expression of BLyS and its receptors
in B-cell non-Hodgkin lymphoma correlation with
disease activity and patient outcome. Blood
20041042247-53. 4. He B, et al. Lymphoma B
cells evade apoptosis through the TNF family
members BAFF/BLyS and APRIL. J Immunol
20041723268-79. 5. Endo T, et al. BAFF and
APRIL support chronic lymphocytic leukemia B-cell
survival through activation of the canonical
NF-kappaB pathway. Blood 2007109703-10.