Stringent thiol-mediated retention in B lymphocytes and Xenopus oocytes correlates with inefficient IgM polymerization.
Thiol-dependent retention mechanisms involving the microsecond chain Cys575 ensure that only polymeric IgM are secreted. B lymphocytes are unable to polymerize IgM and degrade unpolymerized precursors intracellularly. Since several non-lymphoid transfectants secrete hexameric IgM, specific mechanism(s) inhibiting IgM polymerization/secretion may be active in B cells. Here, we show that Xenopus laevis oocytes are also unable to polymerize IgM and retain this isotype via Cys575 as efficiently as B cells. The mechanisms and the hierarchy of the thiol-dependent pre-Golgi retention are conserved in amphibian oocytes, as indicated by the efficient retention of secretory IgA and the slow secretion of unassembled J558 lambda chains. We also show that B cells do not lack any structural component necessary to polymerize IgM: after retention has been weakened by 2-mercaptoethanol, polymerization can occur if oxidizing conditions are restored. Since release from retention can result in polymerization, stringent retention in B cells and oocytes might be at the basis of their common inability to polymerize secretory IgM. Our findings suggest that disulfide interchange reactions in the exocytic compartment can be modulated during B cell differentiation to control IgM secretion.
Carelli
S
S
DIBIT, Scientific Institute San Raffaele, Milano, Italy.
Ceriotti
A
A
Sitia
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D003545:Cysteine / Q000502:physiology; D006026:Glycoside Hydrolases / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A / Q000187:drug effects / Q000378:metabolism; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism; D016393:Lymphoma, B-Cell; D009865:Oocytes / Q000276:immunology / Q000378:metabolism*; D010950:Plasma Cells / Q000378:metabolism; D011108:Polymers; D012313:RNA / Q000096:biosynthesis; D019163:Reducing Agents / Q000494:pharmacology; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D007070:Immunoglobulin A; D007075:Immunoglobulin M; D007146:Immunoglobulin lambda-Chains; D011108:Polymers; D019163:Reducing Agents; D013438:Sulfhydryl Compounds; C024242:polymeric IgM; D012313:RNA; D006026:Glycoside Hydrolases; D003545:Cysteine