Activation of B-cells by sIgM cross-linking induces accumulation of CD5 mRNA.
The surface membrane molecule CD5 is expressed on mature T cells and on the B-1a subpopulation of B cells. These CD5 positive B cells express an antibody repertoire with a relatively high frequency of self-reactivity. There is uncertainty about the origins of CD5 B cells and the reasons for this are reviewed. Recent reports which relate to the lineage/selection debate are discussed. For instance, an increase in the frequency of CD5 B cells is a feature of several genetically determined polysystem autoimmune syndromes. In the case of motheaten (me, mev) the pathogenesis of this increase in CD5 B cells is not yet understood, even though the mutation has been mapped to the Hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Another mutation which affects B cell development, X-linked immunodeficiency (xid), encodes a point mutation in a B cell cytoplasmic tyrosine kinase. Expression of xid in otherwise normal mice causes a lack of CD5 B cells and a shift in the antibody repertoire. Interestingly, expression of both xid and motheaten results in an amelioration of autoantibody production. Evidence is presented that in B cells regulation of expression of CD5 can occur at the level of mRNA and that cross-linking of sIgM can induce the accumulation of CD5 mRNA. The overall concept advanced is that cells expressing natural autoantibodies are triggered via sIgM ligation to become CD5 B cells.
Bandyopadhyay
R S
RS
Tufts University School of Medicine, Boston, MA.
Teutsch
M R
MR
Wortis
H H
HH
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D001327:Autoimmune Diseases / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001483:Base Sequence; D018956:CD5 Antigens; D005786:Gene Expression Regulation; D007107:Immune System / Q000196:embryology; D007075:Immunoglobulin M / Q000276:immunology*; D007152:Immunologic Capping / Q000502:physiology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics
D015703:Antigens, CD; D018956:CD5 Antigens; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse