Strain differences in the immune response of mice to homologous sperm-specific lactate dehydrogenase (LDH-C4).

The sperm-specific isozyme of murine lactate dehydrogenase (LDH-C4) was injected into female mice of various strains. Two regulatory phenotypes characterize the resultant immunity to LDH-C4: one is manifested by high, intermediate or low levels of response, the other by the immediate or delayed maturation of peak titer. The response of several strains can be classified as high (SWR, SJL, BABL/c, C3H/He) and intermediate to low (A, CBA, DBA/2, DBA/1, C57BL/6) according to the level of antibody production and cell mediated immunity. BALB/c, SJL and SWR strains are immediate responders while DBA/2 and C3H/He mice are clearly delayed responders. Maturation and magnitude of response do not appear to be related. Both the antibody and cell mediated responses are T-dependent, but are not obviously associated with Ig allotype or H-2 regulation.     

Isoenzyme pattern of HPRT in murine erythrocytes: Control by an autosomal locus

A locus on chromosome 7 controls the electrophoretic mobility of hypoxanthine phosphoribosyltransferase (HPRT) isoenzymes in mouse erythrocytes, but not in several other tissues. This locus is designated Hma (HPRT mobility alteration) and maps very close to the Hbb locus. The A/J, AKR/J, AU/SsJ, BALB/cJ, CBA/J, C3H/HeJ, DBA/2J, LP/J, RF/J, SEA/Gn, ST/BJ, and 129/J strains and our population of Swiss albino mice have the Hmaa allele. Hmaa is dominant to Hmab, which is found in the C57BL/6J, C57BL/KsJ, C58/J, LT/Sv, MA/MyJ, SJL/J, and SWR/J strains. Both alleles are found in feral Mus musculus. In our conditions, homozygotes for Hmab have two major bands of HPRT activity after electrophoresis of extracts of erythrocytes and of other tissues. Heterozygotes and Hmaa homozygotes have three bands in erythrocyte extracts but two band in other tissues.     

A new mouse lymphoid alloantigen (Lgp100) recognized by a monoclonal rat antibody

A new genetically polymorphic cell surface antigen recognized by a monoclonal rat anti-mouse antibody is expressed on mouse lymphoid cells. Fluorescence analysis on the fluorescence-activated cell sorter (FACS) locates the antigen on thymocytes, lymph node cells, and both T and B cells in the spleen. It also appears on approximately 40% of cells in the bone marrow.Immune precipitations from surface iodinated spleen cells followed by 2-D gel electrophoresis demonstrate that the antigen is a glycoprotein of approximately 100,000 daltons. Since it is expressed in all lymphoid tissues and on both T and B cells, we designate it lymphoid glycoprotein 100 (Lgp100).Strains with Lgp100 include A/J, AKR/J, AKR/Cu, BALB/c, 129/J, CBA/N, C3H/HeJ, CBA/2J, and SJL/J. Strains with no detectable antigen include C57BL/6J, C57BL/10J, C57BR/cdJ, C57L/J, and C58/J. Intercrosses and backcrosses establish a pair of alleles, a positive and a negative one, at a single locus. Heterozygotes display about 50% as much antigen as homozygotes by quantitative membrane immunofluorescence on the FACS. Tests for Lgp100 in 35 recombinant inbred strains from three crosses (CXB, BXB, and BXH) locate this locus on chromosome 1, closely linked to theMls locus.     

Nematospiroides dubius: genetic control of immunity to infections of mice

Inbred strains of mice differ in their susceptibility and resistance to challenge infections with Nematospiroides dubius. In our studies, F1 hybrid mice from resistant SJL and susceptible CBA parents were resistant to N. dubius challenge infections. Only 22% of backcrosses to SJL were susceptible while backcrosses to CBA had a wide range of susceptibility. Male mice were more susceptible than female mice. In another experiment, inbred strains of mice were compared in their ability to resist N. dubius challenge infection: SJL and A.SW (H-2s) mice became resistant after one immunizing infection, A, A/He (both H-2a), as well as BALB/c and DBA/2 (both H-2d) mice became resistant after two immunizing infections, while C57BL/6 (H-2b), C3H/He, CBA, and AKR (H-2k) mice remained susceptible. The resistance to reinfections was characterized by reduction of worm burdens between Days 6 and 14 postinfection. It was concluded that (1) resistance to N. dubius challenge infections is inherited in a dominant fashion and that multiple genes may influence such response, which in turn might be modulated by the Y chromosome; (2) both MHC and non-MHC genes may influence, in conjunction with the number of exposures to parasite antigens, the resistance to challenge infections.     

Influence of the immunoglobulin heavy chain locus on expression of the VK1GAC light chain

The VK1GAC light chain represents the dominant V kappa structure employed in the antibody response of A/J mice to streptococcal group A carbohydrate ( GAC ). Two anti-idiotypic antisera, anti- Id5 and anti- Id20 , with specificity for the VK1GAC light chain were used to examine anti- GAC antibody responses in a series of inbred mouse strains that differ at the heavy chain constant region ( IgCH ) allotype locus. Both idiotypes were expressed in normal and immune sera from mice of most IgCH allotypes, except IgCHb (C57BL/6J) and IgCHf (CE/J). C57BL/6J mice expressed Id5 , but not Id20 , whereas CE/J mice did not express either idiotype. Testing of recombinant inbred strains between BALB/c and C57BL/6 indicated that the pattern of idiotype expression did not correlate with IgCH allotype. The C X B recombinants expressed all three idiotype patterns that were observed in the panel of inbred strains. Testing of allotype congenic mice between BALB/c and C57BL/6 showed that CB.20 and BC.8 mice were Id20 -, whereas BAB-14 mice were Id20 +, indicating that both VH and background (V kappa or regulatory) loci must be derived from BALB/c to obtain Id20 expression. The difference in the frequency of idiotype expression observed between BALB/c and BAB-14 mice indicates that the IgCH locus may exert a quantitative influence on the expression of this light chain. To examine the Id20 -, Id5 + antibodies of C57BL/6 mice, anti- GAC hybridomas were prepared. Of 16 C57BL/6-derived anti- GAC monoclonal antibodies, six were reactive with anti- Id5 and not with anti- Id20 . Isoelectric focusing of the purified kappa light chains from three of these antibodies revealed two distinct spectrotypes that co-migrated with the two known VK1GAC spectrotypes observed with A/J anti- GAC light chains. Idiotypic analysis of in vitro recombinants between the heavy and light chains of A/J and C57BL/6 monoclonal antibodies demonstrated that the C57BL/6 light chains were idiotypically similar to A/J light chains when they were free in solution or paired with A/J heavy chains. These results demonstrate that C57BL/6 mice can express a light chain that is very similar, if not identical, to the VK1GAC light chain, although the light chain is expressed in lower frequency and is paired with a distinct VH structure, which can mask expression of one of the VK1GAC idiotypes. These effects on V kappa expression map to at least three genetic loci: VH, CH, and an unlinked locus.     

Strain differences in the development of auto-anti-idiotypic antibody regulation with age: genetic linkage to the Igh-C locus

The effect of age on the appearance of anti-idiotype (Id)-blocked, hapten-augmentable plaque-forming cells (PFC) in various strains of mice was investigated. Strains of mice at 2 and 6-11 months of age were immunized with 500 micrograms trinitrophenylated bovine gamma-globulin (TNP-BGG) in complete Freund's adjuvant (CFA) intraperitoneally. Splenic IgM and IgG anti-TNP PFC responses were assayed for anti-Id-blocked, hapten-augmentable PFC 14 days after immunization. It was found that strains differ with regard to the age at which they produce anti-Id-blocked, hapten-augmentable PFC. C57BL/6J (B6), DBA/1J, and C3H/HeJ mice produced a significantly high percentage of hapten-augmentable IgG anti-TNP PFC at 8-9 months of age as compared with the 2-month-old group. In contrast, 129/J, AKR/J, and C57L/J mice produced a significantly low percentage of hapten-augmentable PFC at 6-7 months of age as compared with the 2-month-old group. The CBA/J mice were high-hapten-augmentable plaque producers at both 2 and 7 months of age. SJL/J mice were, on the other hand, low producers at 2 and 11 months of age. Immune sera from high hapten-augmentable plaque-producing strains caused a hapten-reversible block of plaque formation by spleen cells from TNP-BGG-immune C57BL/6J mice and also revealed anti-(anti-TNP F(ab')2-IgG) titer as assayed by passive hemagglutination. This PFC-inhibiting activity in the immune sera of old C57BL/6J mice was an antibody of the IgG2a and IgG3 classes, lacked anti-TNP antibody activity, but reacted with anti-TNP antibody of C57BL/6J origin. Genetic analysis between high hapten-augmentable plaque production and allotypes in the (129/J X B6) crosses of the same H-2b haplotypes revealed that all of the backcrosses and F2 with high hapten-augmentable plaque production had the Igh-1a allele of the high-producer, 129/J mouse. In contrast, the crosses with low hapten-augmentable plaque production were homozygous for the Igh-1b allele of the low-producer, B6 mouse. The data suggest strain differences in the development of auto-anti-idiotypic antibody regulation with age which may be controlled by a gene(s) linked to the Igh-C locus.     

AKR/J gene(s) unlinked to H-2 determines dominant inheritance of lymphocyte hyporesponsiveness to acetylcholine receptor

Mice with the H-2b major histocompatibility complex haplotype are high immune responders to nicotinic acetylcholine receptors (AChR), whereas mice with the H-2k haplotype are generally low responders. F1 progeny of C57BL/6 (H-2b) mice crossed with mice of most H-2k strains are high responders to AChR in standard conditions of testing helper T cell proliferation in vitro (4 X 10(5) lymph node cells/microwell, 1 wk after primary challenge in vivo). In contrast, the F1 progeny of AKR/J (H-2k) crossed with high responder (H-2b) strains (B6, A.BY, or C3H.SW) were all hyporesponsive to AChR when lymphocytes were tested at 4 X 10(5) cells/well. However, at a density of 1 X 10(6) or greater/well, a high level of antigen-specific responsiveness was demonstrable in the F1 hybrid lymphocytes. A shift from low to high responsiveness to AChR at high cell densities was observed also in the H-2b strain AKR.B6. Other strains previously demonstrated to be low responders to AChR did not become responsive to AChR when lymphocyte numbers were increased to 1.4 X 10(6)/well. The N2 generation yielded by backcrossing (AKR X B6)F1 mice to AKR/J were all low responders, whereas N2 progeny derived by backcrossing F1 to B6 were high or low responders in a ratio of approximately 1:1 (independent of their H-2 phenotype). Results consistent with this observation were obtained in (AKR X B6) F2 mice. These data suggest that at least one AKR/J gene outside of the H-2 complex exerts a hyporesponsive influence on the I-A-dependent helper T cell response to AChR in H-2b mice.     

Immunity to leprosy. II. Genetic control of murine T cell proliferative responses to Mycobacterium leprae

T cell proliferative responses to Mycobacterium leprae were measured after immunization of mice at the base of the tail with antigen and challenging lymphocytes from draining lymph nodes in culture with M. leprae. This T cell response to M. leprae has been compared in 18 inbred strains of mice. C57BL/10J mice were identified as low responder mice. The congenic strains B10.M and B10.Q were found to be high responders, whereas B10.BR and B10.P were low responders. F1 (B10.M X C57BL/10J) and F1 (B10.Q X C57BL/10J) hybrid mice were found to be low responders, similar to the C57BL/10J parent, indicating that the low responsive trait is dominant. Whereas B10.BR mice were shown to be low responders to M. leprae, B10.AKM and B10.A(2R) were clearly high responders, indicating that the H-2D region influences the magnitude of the T cell proliferative response. Gene complementation within the H-2 region was evident. Genes outside the H-2 region were also shown to influence the response to M. leprae. C3H/HeN were shown to be high responder mice, whereas other H-2k strains, BALB.K, CBA/N, and B10.BR, were low responders. Gene loci that influence the T cell proliferation assay have been discussed and were compared to known background genes which may be important for the growth of intracellular parasites. Because mycobacteria are intracellular parasites for antigen-presenting cells, genes that affect bacterial growth in these cells will also influence subsequent immune responses of the host.     

Genetic differences in BCG-induced resistance to Schistosoma mansoni are not controlled by genes within the major histocompatibility complex of the mouse.

Induction of nonspecific resistance to Schistosoma mansoni infection after the i.v. injection of viable BCG was investigated in outbred mice and a panel of inbred and H-2 congenic strains. Significant protection was induced in CF1, A/J, C57BL/6, C57BL/10, DBA/2, C57BR, and SJL mice. BALB/c mice were not protected whereas CBA and C3H mice expressed intermediate degrees of protection. Expression of the protective phenomenon is not controlled by genes within the MHC as shown by the marked differences in response between BALB/c and DBA/2 (H-2d) as well as between C57BR and C3H (H-2k) mice. H-2 congenic strains with C57BL/10 background (B10.A and B10.D2) were high responders. BALB.B10 mice carrying the high responder (B10) MHC on the nonresponder (BALB/c) background were not protected. The degree of splenic hypertrophy did not correlate with the expression of nonspecific resistance. These results demonstrate that, in addition to controlling specific immune responses, genetic differences influence the nonspecific protective phenomena related to BCG administration as well.     

Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor

Repeated immunization of normal C57L/J (H-2b) mice with peripheral T cells from BALB.B (H-2b) mice results in the production of antibodies which react with the T cell receptor. A monoclonal antibody-producing hybridoma, F23.1, was isolated from immunized C57L/J mice showing this property. This monoclonal antibody recognizes approximately 25% of peripheral T cells in BALB mice. It stains approximately the same fraction of T cells and precipitates the same heterodimer as the rat monoclonal antibody described previously that was made against isolated receptor material. The allotypic determinant recognized by this monoclonal antibody is present in most common laboratory strains (BALB, C57BL, CBA, A, DBA, C3H) and is absent in C57L, C57BR, and SJL mice. Sorting peripheral T cells from BALB.B or (SJL X BALB/c)F1 mice for the F23.1+ and F23.1- subsets revealed that both populations contain approximately the same CTL precursor frequency for alloantigen. Thus, the T cell receptor allotype defined by F23.1 is present on CTL. Furthermore, cytotoxicity mediated by an F23.1+ CTL line could be blocked specifically by the F23.1 monoclonal antibody. Under appropriate conditions, the monoclonal antibody F23.1 bound to Sepharose 4B beads can induce resting peripheral T lymphocytes of allotype-positive strains to proliferate.     

Genes of the H-2 complex regulate the antibody response to murine leukemia virus

The influence of the major histocompatibility complex of the mouse (H-2 complex) on the antibody response against murine leukemia virus (MuLV) was investigated after 3 different ways of virus presentation (milk transmission of virus, spontaneous virus activation, and immunization with inactivated virus). The antibody response against MuLV was measured in the sera of H-2 congenic C57BL V+ sublines (V+ denotes positive for milk-transmitted MuLV), (B10.AV+ X C57BL)F1 mice, (C57BL X AKR)F1 mice and of C57BL animals after immunization with inactivated AKR virus. The pattern of immune responsiveness of the different C57BL strains to MuLV was independent of virus replication and was similar for the 3 ways of virus presentation. Serum antibody levels were controlled by 2 genes within the H-2 complex. The first gene (Ir-MuLV-1) was located in the I-A region and was complemented by a second gene (Ir-MuLV-2), which was situated in the regions to the right of the I-B region. Presence of 2 responder alleles (Ir-MuLV-1+,2+) led to an optimal antibody response (H-2b haplotype). Animals that only expressed a responder allele in the I-A region (Ir-MuLV-1+,2-) were intermediate responders. Animals lacking a responder allele in the I-A region (Ir-MuLV-1-,2+ or Ir-MuLV-1-,2-) were low responders.     

Cryptosporidium infections in inbred strains of mice.

Cryptosporidium, a protozoan parasite of man and animals, is an important etiological agent of diarrhea throughout the world, particularly in children and immunocompromised individuals such as AIDS patients. Unfortunately, because of the lack of both in vivo laboratory models and reliable in vitro parasite culture systems, virtually nothing is known about the immunological events occurring during disease. In order to identify reliable animal models for infection, we studied C. parvum infections in 19 different strains of mice representing 12 H-2 haplotypes: A/J, AKR/J, B10.D2/J, B10.M/J, C3H/HeJ, C57BL/65, C57BL/6J-bgJ, CBA/NJ, DBA/1J, DBA/2J, HRS/J, HTG/J, NZB/B1NJ, NZW/J, P/J, RIII/J, SJL/J, SWR/J, and WB/ReJ, and in one gerbil: Meriones unguiculatus. Fecal samples and histological sections of the intestine taken on day 7 post-Cryptosporidium inoculation indicated that only the beige mouse (C57BL/6J-bgJ) harbored significant numbers of parasites compared to the other strains. The numbers of parasites harbored in these NK cell-deficient beige mice were, however, considerably lower than those seen in neonatal mice. Adult inbred mouse strains susceptible to Cryptosporidium infections are discussed.     

Strain variations in anti-sperm antibody responses and anti-fertility effects in inbred mice

This study provides evidence for polygenic controls of antisperm antibody levels in inbred male mice immunized with syngenic testis and epididymis. H2-linked and non-H2-linked genes were involved. Mice of H-2d haplotype were high responders, whereas those with H-2k haplotype were nonresponders; however, B10.D2/nSnJ mice (H-2d) were also nonresponders. In vitro fertilization inhibition by antisera correlated positively with the serum antisperm antibody levels, particularly with antibody of the immunoglobulin (Ig) G class. Inheritance of antibody response that inhibited in vitro fertilization (IVF) was an autosomal dominant trait, but this was not apparent for the control of antibody levels per se. Since IVF was inhibited by both IgG and fragment antigen-binding (Fab) isolated from immune sera, but not by immune IgG previously absorbed by sperm or testis, the biologic effect is antigen-specific and probably involved blockade of functional antigenic epitopes. Antisera to testis, caput sperm or cauda sperm were found to inhibit IVF to a similar degree. Inbred strains of mice that produced the highest levels of serum antisperm antibodies that inhibited IVF were A/J, SJL/J, DBA/1J and BALB/cByJ mice, and their antisera immunoprecipitated a common sperm antigen molecule of 35,000 to 40,000 Mr. In contrast, C57BL/6 and C57BL/10 mice produced significant antibody levels that had no effect on IVF, and their sera did not react with the 35,000- to 40,000-Mr peak. Moreover, among BALB/c H-2 congenic mice, only antiserum of responder BALB/cByJ (H-2d) mice immunoprecipitated the 35,000- to 40,000 Mr peak. Thus the 35,000- to 40,000-Mr protein may be of functional significance in the fertilization process.     

Genetic control of immune responses to the 18-kDa protein of Mycobacterium leprae. Different TH1 subsets may be involved in proliferative and delayed-type hypersensitivity responses.

In vitro and in vivo responses to the 18-kDa protein of Mycobacterium leprae have been analysed in different strains of mice. Lymphocytes from BALB/cJ (H-2d), BALB.B (H-2b), B10.BR (H-2k), and B10.M (H-2f) mice primed with 18-kDa protein yielded high T cell proliferative responses, while those from C57BL/10J (H-2b) mice yielded lower responses. Both H-2 and non-H-2 genes contributed to the magnitude of responsiveness. F1 mice from high and low responder strains showed high responsiveness to the 18-kDa protein. Supernatants from lymph node cell cultures prepared from 18-kDa protein-immunised BALB/cJ, B10.BR, and C57BL/10J mice contained IL-2 but no IL-4, indicating that activated T cells from both high and low responder mice were of a TH1 phenotype. Cell cultures from low responder C57BL/10J mice produced less IL-2 than those from high responders. The low responsiveness to the 18-kDa protein in proliferative assays might be due to a low frequency of antigen-specific T cells in the C57BL/10J mouse strain. BALB/cJ, C57BL/10J, and F1 (BALB/cJ x B10.BR) mouse strains were tested for in vivo DTH reactions to the 18-kDa protein. All strains, including C57BL/10J, were high DTH responders. Although DTH effector cells and 18-kDa protein-specific proliferative T cells belong to the TH1 subset, our data comparing high and low responder status indicate that distinct TH1 subpopulations are stimulated in response to the 18-kDa protein of M. leprae.     

Strain variation in BCG-induced chronic pulmonary inflammation in mice. I. Basic model and possible genetic control by non-H-2 genes.

C57BL/6 mice (haplotype H-2b) responded in a dose-dependent fashion to killed BCG by marked enlargement of the spleen and lung. Neither CBA nor C3H mice (haplotype H-2k) responded to such treatment. Pulmonary inflammation in responder B6 animals was characterized by a marked chronic interstitial and alveolar granulomatous process, and was accompanied by occasional granulomata, hyperemia, and loss of architecture in the spleen. Inflammation in non-responder CBA and C3H animals was minimal in both the lung and spleen. The response does not appear to be controlled by genes within the major histocompatibility complex, but is associated with a C57 background. B10.BR mice (responder background, H-2k) were responder animals and C3H.SW mice (nonresponder background, H-2b) were nonresponders. In addition, all animals tested with a C57 background were responders even though two of these strains were not H-2b (C57BL/Ks, H-2d and C57Br/cd, H-2k). The resolution of the mechanism of genetic control of this response in mice may provide information relevant to possible genetic control of chronic pulmonary inflammation in man.     

Interstrain differences in mice in developing migration inhibition factors to Candida albicans antigens

The authors studied the time course of MIF production by lymphocytes of CBA (H-2k), C57BL/6J (H-2b) and (CBA X C57BL/6J) F1 (H-2b/H-2k) mice sensitized to Candida albicans antigens. The interstrain differences in lymphokin production were identified, CBA mice appeared to be highly responsive, whereas C57BL/6J to be low-responsive. Partial hybridological analysis made it possible to ascertain the presence of the dominant type heredity of high MIF production in response to Candida albicans antigens.     

Murine responses to (Tyr-Glu-Ala-Gly)n: II. H-2 and non-H-2 gene effects

Mice of the H-2^b haplotype responded to the sequential polymer poly(Tyr-Glu-Ala-Gly) in the in vitro T-cell proliferative assay, irrespective of whether they were homozygous or heterozygous at the H-2^b locus. The antibody responses of the H-2^b congenic mice to this polymer were variable, with A.BY and BALB.B showing responses better than those of C57BL/6 and C57BL/10 strains. The antibody responses of the F₁ progeny of (responder × nonresponder) strains of mice to this polymer are generally lower than the responder parents. F₁ mice with C57BL/10 background were the poorest responders. Studies with F₂ mice and backcross progenies of selective breeding of high and low antibody responder (C57BL/6 × BALB/c) F₁ to high responder C57BL/6 mice indicated that both non-H-2 genes and H-2 gene dosage effects influenced the magnitude of the humoral antibody responses. Animals having low responder non-H-2 background and only half the dosage of the responder immune response genes has greatly diminished antibody responses.     

Effect of genotype and day or night time of testing on mice behavior in the light-dark box and the open-field tests

The light-dark box (LDB) and the open-field (OF) tests are widespread experimental models for studying locomotion and anxiety in laboratory rats and mice. The fact that rodents are nocturnal animals and more active at night raises a critical question of whether behavioral experiments carried out in the light phase are methodologically correct. Parameters of behavior of four mouse strains (C57BL/6J, DBA2/J, AKR/J and CBA/LacJ) in the light-dark box and open-field tests in the light and dark phases were compared. No significant influence of the phase of testing on anxiety in LDB and OF tests was revealed. In the OF test CBA mice showed increased locomotor activity, whereas AKR and C57BL/6 mice showed increased defecation in the dark phase. It was concluded that: 1) the phase of testing is not crucial for the expression of anxiety in LDB and OF; 2) the sensitivity to the phase of testing depends on the genotype; 3) the indices of behavior in the genotypes sensitive to the phase of testing (locomotion in the CBA and defecation in the AKR and C57BL/6 mouse strains) are increased in the dark phase.     

BALB/c antiarsonate idiotypes: Gene complementation necessary for expression

The expression of two idiotype (id) families (5AF6 and 3C6) associated with the BALB/c p-azophenylarsonate-specific antibody response was examined in 11 mouse strains. Eight strains produced some of one or the other of these two id families with the mean percent expression in the anti-Ar responses of id(+) strains ranging from 8 to 43% for the 5AF6 and from 2 to 10% for the 3C6 idiotype. Four strains of mice (C58, AKR, PL, and RF) thought to have Lyt-3.1-linked V_L repertoire differences from other mouse strains (Lyt-3.2) were tested for their capacity to contribute to 5AF6 and 3C6 id expression. The RE strain was capable of producing 5AF6 id and small amounts of 3C6 id. Tests of Lyt-3.1 congenic strains C.AKR (AKR Lyt-3.1 on a BALB/c background) and C.C58 (C58 Lyt-3.1 on a BALB/c background) showed that C.AKR could produce 5AF6 id while C.C58 could not. 3C6 id expression was present but depressed in C.C58 mice compared with the high 3C6 id expression in C.AKR. Breeding studies mating C.C58 (bearing the required Igh-C^a-linked V _H genes) to other 5AF6(–) strains showed that gene complementation could result in 5AF6 expression in F₁ offspring. 5AF6(–) strains capable of complementation included CBA/J, C57BL/6J, AKR/J, and PL/J. C58/J (from which C.C58 were derived) was the only tested strain that failed to complement for 5AF6 id expression. Additional matings between C58/J[5AF6(–)] and CBA/J[5AF6 (–)] showed F1 offspring could produce 5AF6 id, indicating that C58/J can contribute functional V _H genes necessary for 5AF6 id expression. Depressed expression of 5AF6 and 3C6 id was noted in mice where the C58/J-derived Lyt-3.1 genotype was present. The possibility that the depression of 5AF6 and 3C6 id expression derived from C58/J mice was due to regulatory influences rather than a lack of the V _L structural genes is discussed.Abbreviations used in this paper Ar p-azophenylarsonate - DNP dinitrophenol - H heavy - HIS hyperimmune suppressed - id idiotype - Ig immunoglobulin - IEF isoelectric focusing - k kappa - L light - PC phosphorylcholine - S.D. standard deviation     

Serum antibody and cellular immune response in mice to dextran B512.

Serum antibodies to dextran started to appear 3 days after immunization of C57BL/6 mice. Synthesis of IgM antibodies was followed by IgG3 and IgGA. Other immunoglobulin classes (IgG1, IgG2b, and IgG2a) were very low or absent. The immune response to dextran was also thymus independent with regard to IgG3 and IgA synthesis as demonstrated by the use of nu/nu mice. CBA and C57BL/6 mice were high responders to dextran with regard to IgM synthesis. C57BL/6 mice produced high levels of IgG3 and IgA antibodies, whereas CBA, A/J, and A.TL only synthesized IgM antibodies. A/J and A.TL strains were most frequently low responders with regard to IgM synthesis and CBA/N mice were completely nonresponders with regard to all immunoglobulin classes. The ability to produce anti-dextran antibodies increased with age in high responder strains. This was most pronounced for IgG3 and IgA antibodies, which reached adult levels 3 months after birth. The affinity of anti-dextran antibodies was high and homogeneous in antisera from C57BL/6 mice. Preimmune matural antibodies and antibodies from immunized low responder strains had a low and variable affinity for dextran.