I GM Degradation in b cells: er and post-er in iitro localizations

D. Winitz, A. Kerem, Y. Elkabetz, S. Bar-Nun

Research output: Contribution to journalArticlepeer-review

Abstract

hnmunoglobulin M (IgM) exhibits distinct fates during B (:ell differentiation: in pre-B cells IgM μ heavy chains art not expressed;B cells display membrane mlgM, while secretory slgM is not secreted and is degraded; plasma (:ells secrete polymeric slgM. We discovered that slgM rapid degradation occurred in 38C B cells at a novel site. Upon blocking protein exit from the Et{, either by brefeldin A (Bt:A) or by plasma membrane perlneabilization, the selective slgM degradation was strongly inhibited. This degradation was reconstituted in vitro if prior to permeabilization transport was allowed or upon in vitro transport reconsfitution in permeabilized cells, as indicated by mIgM maturation.Finally. slgM-containing transport vesicles were generated and isolated. This postER degradation does not comply with ER quality control that retains and eliminates abnormal, unfolded or partially assembled proteins, ttowever, this latter mechanism operated in 70Z/3 pre B cells, in light (L) chain deficient Etl cells or upon complete reduction of II-L bond with thiols in 38C B cells, where free /1 chains were degraded in the Ell of BFA-treated or permeabilized (:ells. Under these conditions, transport vesicles were devoid of μ. Never( heless, this quality control degradation was no longer restricted to secretory ts or to B cells, as it also eliminated membrane μm and took place in ER of plasma ceils. Conversely, upon L chain indu(:tion by LPS in 70Z/3 cells, ps L was s(qectively degraded by a transport-dependen! post-ER mechanism. Our data suggest that a motif which direcls I chains Io ER degradation is mask('d by L chain. hence allowing anolher motif to direct jzs L to post-Ell degradation.

Original languageEnglish
Pages (from-to)A930
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997

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