title: The xid mutation diminishes memory B cell generation but does not affect somatic hypermutation and selection.
abstract: In this study, we examine the relationship between primary and secondary T cell-dependent immune responses using the response of xid mice to the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) as an experimental model. The reduced serologic primary immune response of xid mice was demonstrated to be caused by a substantially decreased Ab-forming cell (AFC) generation. Furthermore, the germinal center reaction in the primary xid immune response was diminished and the frequency of NP-specific memory B cells prior to secondary immunization was reduced 10-fold. Despite the poor primary response of xid mice, secondary exposure to Ag generated a response that was qualitatively and quantitatively equal to that of wt mice. The number of IgG1 AFCs in spleen and bone marrow increased equally in both groups, as did the proportion of AFCs secreting high affinity Ab in both locations. The extent and distribution of somatic mutations in the V(H) genes of xid secondary response B cells was also found to be normal, indicating that the xid gene product is not critical for the processes that result in affinity maturation. Thus, although xid mice generate memory B cells of normal phenotype but at a substantially lower frequency, this does not limit the magnitude of the secondary response. Therefore, our results imply that the reduced memory B cell frequency in xid mice is still above some threshold value necessary for a normal secondary immune response.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Ridderstad
authors.forename: G J
authors.initials: GJ
authors.lastname: Nossal
authors.forename: D M
authors.initials: DM
authors.lastname: Tarlinton
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D051940:B7-2 Antigen; D023201:CD40 Ligand; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D008040:Genetic Linkage; D006241:Haptens / Q000008:administration & dosage; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D009154:Mutation; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D014162:Transfection; D014960:X Chromosome / Q000235:genetics
chemical_list: C098951:4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin; D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D006241:Haptens; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D023201:CD40 Ligand; D006433:Hemocyanins