Vasoactive intestinal peptide induces S(alpha)/S(mu) switch circular DNA in human B cells.
Vasoactive intestinal peptide (VIP), a major neurotransmitter of peripheral nerves, has been suggested to function in host defense by regulating local human immune function. Indirect evidence has been marshaled that VIP can function as a switch factor for IgA in human Ig isotype recombination. In this study we directly tested the ability of VIP to function as a factor driving human B cells into IgA producing cells by assessing its ability to induce switch circular DNA representing direct mu to alpha switching. In addition we determined the generation of alpha germ-line transcripts and measured the level of IgA protein produced. Stimulation with VIP and CD40 mAb induced IgA production by human IgD+ B cells while VIP or CD40 alone failed to do so. Stimulation of purified IgD+ B cells with VIP plus CD40 mAb induced generation of switch circular DNA representing in vitro driven isotype switching from mu to alpha. CD40 mAb alone induced alpha germ-line transcripts but not IgA switch circles. Thus VIP, a neurogenic factor, can induce alpha-specific switching in CD40-activated human B cells and may thereby play an important role in directing the humoral immune response at mucosal surfaces.
Fujieda
S
S
The Hart and Louise Lyon Laboratory, Division of Clinical Immunology/Allergy, UCLA School of Medicine, Los Angeles, California, USA.
Waschek
J A
JA
Zhang
K
K
Saxon
A
A
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004270:DNA, Circular; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching / Q000187:drug effects* / Q000235:genetics; D007072:Immunoglobulin D / Q000096:biosynthesis; D007137:Immunoglobulin alpha-Chains; D007148:Immunoglobulin mu-Chains; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D019013:CD40 Antigens; D004270:DNA, Circular; D007070:Immunoglobulin A; D007072:Immunoglobulin D; D007137:Immunoglobulin alpha-Chains; D007148:Immunoglobulin mu-Chains; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide