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B-cell activation and HIV-1 infection
i!i!i!iiiligii!i day 14 and early secondary anti* oxazolone antibodies are 2.58 and 3.66 per 1000 bases, respectively, which indicates an accumulation of silent mutations after day 14. However, if one examines the absolute values used to arrive at these frequencies, namely 10 silent mutations per 4200 bases at day 14 and 11 silent mutations per 3000 bases for secondaries 1, it is difficult, to my mind, to be convinced of an increasing trend. Indeed, C4sar Milstein states in the original discussion of these data that "... the number of silent mutations that can be computed is rather low for accurate calculations" 1. C4sar Milstein's mention of the
current controversy about whether mutation can be re-induced during anamnestic responses is a point well taken. As he discusses, there is evidence from several laboratories that mutation is turned off prior to such responses. If, as Milstein believes, mutation can be re-induced many times in anamnestic responses, then I agree that a mutation and selection mechanism whose efficiency is limited by the rate of B-cell division could adequately account for much of the available data. However, ! feel that the question of whether the reinduction of mutation can occur has yet to be tested adequately. Moreover, some of the data that we 2 and others 3 have obtained are difficult
to explain by a mutation-selection model in which the rate of B-cell division is limiting, even if mutation can be re-induced in anamnestic responses.
B-cell activation and HIV-1 infection
phenomenon in the course of Toxoplasma gondii infection. The specific antibody secretion was always correlated with the acute stage of infection and disappeared about 20 weeks after the seroconversion (unpublished data). For these reasons, it can be supposed that this phenomenon results from the antigen stimulation of the immune system. In the case of HIV infection, it was suggested that the steady HtVspecific B-cell activation might reflect the antigenic stimulation due to the persistence of HIV replication 7. Spontaneous in vitro secretion of anti-mumps antibodies in HIVinfected patients seropositive for mumps virus was investigated 6. None of these patients secreted antibodies to mumps virus (a virus that does not persist in the host) and this result argues against an in vivo polyclonal B-cell activation mechanism. It could, therefore, be proposed that in vitro HIV-l-specific antibody production by PBLs reflects the chronicity of HIV infection.
Valle, G.P. et al. (1988) Clin. Immunol. Immunopathol. 46, 342-351 2 Vendrell, J.P., Reynes, J., Rabesandratana, H. et al. (1988) Lancet ii, 278-279 3 Stevens, R.H., Macy, E., Morrow, C. et al. (1979) J. Immunol. 122, 2498-2504 4 Fons, G., Uytehagg, C.M., Loggen, H.G. et aI. (1985) J. Immunol. 135, 3094-3101 5 Kantele, A.M., Tanaken, R. and Arvilommi, H. (1988) J. Infect. Dis. 158, 1011-1116 6 Segondy, M., Vendrell, J.P., Reynes, J. et al. (1990) Eur. J. Clin. MicrobioI. Infect. Dis. 9, 745-750 7 Lee, F.K., Nahmias, A.J., Lowery, S. et al. (1989) AIDS Res. Hum. Retroviruses 5, 517-523
Secretion of antibodies against HIV-1 antigens by peripheral blood lymphocytes (PBLs) m vitro is observed in all HIV-l-infected patients 1,2. The persistent character of HIV-l-specific B-cell activation contrasts with the transient in vitro specific antibody production described in several models of immunization of acute infections 3-5. Possible mechanisms that are responsible for this steady activation of B ceils in HIV-1 infection were recently summarized by A. Amadori and L. Chieco-Bianchi (Immunol. Today, 1990, 11, 374-379). These authors favour the hypothesis that there is a strong specific response to HIV antigens instead of an indiscriminate polyclonal activation or an Epstein-Barr virus immortalization of HIV-specific B-cell clones. We agree with this opinion, which is in accordance with our results obtained in several models of infection. We have studied the in vitro secretion of cytomegalovirus (CMV)specific antibodies in subjects with acute CMV infection and in HIVinfected patients with chronic CMV infection 6. We have observed that the CMV-specific antibody secretion in vitro is transient in patients with acute infection and persistent in subjects with chronic infection. We have also investigated this
J.P. Vendrell M. Segondy A. Serre Laboratoires d'Immunologie et de Virologie, Hdpital Lapeyronie, 555 Route de Ganges, Montpellier 34059 Cedex, France.
References 1 Amadori, A., De Rossi, A., Faulkner-
Immunology Today
94
Tim Manser Dept of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
References 1 Berek, C. and Milstein, C. (1988) Immunol. Rev. 105, 5-26 2 Manser, T. (1989) J. Exp. Med. 170, 1211-1230 3 Wysocki, L.J., Gefter, M.L. and Margolies, M.N. (1990) J. Exp. Med. 172, 315-330
The review by Amadori and Chieco-Bianchi (Immunol. Today, 1990, 11,374-379) in the continuing HIV series, presented many possibilities and mechanisms of B-cell involvement in HIV infection, including the generation of antiCD4 reactivity by anti-idiotypic antibodies. The immune response to the CD4binding site of gp 120 should result in an antibody whose Fab segment has the immunological appearance of the gp120 attachment area on CD4. If this occurs, the monoclonal antibody Leu3a should detect it in an HIV-positive serum.
vol 12 No. 2 1991
current controversy about whether mutation can be re-induced during anamnestic responses is a point well taken. As he discusses, there is evidence from several laboratories that mutation is turned off prior to such responses. If, as Milstein believes, mutation can be re-induced many times in anamnestic responses, then I agree that a mutation and selection mechanism whose efficiency is limited by the rate of B-cell division could adequately account for much of the available data. However, ! feel that the question of whether the reinduction of mutation can occur has yet to be tested adequately. Moreover, some of the data that we 2 and others 3 have obtained are difficult
to explain by a mutation-selection model in which the rate of B-cell division is limiting, even if mutation can be re-induced in anamnestic responses.
B-cell activation and HIV-1 infection
phenomenon in the course of Toxoplasma gondii infection. The specific antibody secretion was always correlated with the acute stage of infection and disappeared about 20 weeks after the seroconversion (unpublished data). For these reasons, it can be supposed that this phenomenon results from the antigen stimulation of the immune system. In the case of HIV infection, it was suggested that the steady HtVspecific B-cell activation might reflect the antigenic stimulation due to the persistence of HIV replication 7. Spontaneous in vitro secretion of anti-mumps antibodies in HIVinfected patients seropositive for mumps virus was investigated 6. None of these patients secreted antibodies to mumps virus (a virus that does not persist in the host) and this result argues against an in vivo polyclonal B-cell activation mechanism. It could, therefore, be proposed that in vitro HIV-l-specific antibody production by PBLs reflects the chronicity of HIV infection.
Valle, G.P. et al. (1988) Clin. Immunol. Immunopathol. 46, 342-351 2 Vendrell, J.P., Reynes, J., Rabesandratana, H. et al. (1988) Lancet ii, 278-279 3 Stevens, R.H., Macy, E., Morrow, C. et al. (1979) J. Immunol. 122, 2498-2504 4 Fons, G., Uytehagg, C.M., Loggen, H.G. et aI. (1985) J. Immunol. 135, 3094-3101 5 Kantele, A.M., Tanaken, R. and Arvilommi, H. (1988) J. Infect. Dis. 158, 1011-1116 6 Segondy, M., Vendrell, J.P., Reynes, J. et al. (1990) Eur. J. Clin. MicrobioI. Infect. Dis. 9, 745-750 7 Lee, F.K., Nahmias, A.J., Lowery, S. et al. (1989) AIDS Res. Hum. Retroviruses 5, 517-523
Secretion of antibodies against HIV-1 antigens by peripheral blood lymphocytes (PBLs) m vitro is observed in all HIV-l-infected patients 1,2. The persistent character of HIV-l-specific B-cell activation contrasts with the transient in vitro specific antibody production described in several models of immunization of acute infections 3-5. Possible mechanisms that are responsible for this steady activation of B ceils in HIV-1 infection were recently summarized by A. Amadori and L. Chieco-Bianchi (Immunol. Today, 1990, 11, 374-379). These authors favour the hypothesis that there is a strong specific response to HIV antigens instead of an indiscriminate polyclonal activation or an Epstein-Barr virus immortalization of HIV-specific B-cell clones. We agree with this opinion, which is in accordance with our results obtained in several models of infection. We have studied the in vitro secretion of cytomegalovirus (CMV)specific antibodies in subjects with acute CMV infection and in HIVinfected patients with chronic CMV infection 6. We have observed that the CMV-specific antibody secretion in vitro is transient in patients with acute infection and persistent in subjects with chronic infection. We have also investigated this
J.P. Vendrell M. Segondy A. Serre Laboratoires d'Immunologie et de Virologie, Hdpital Lapeyronie, 555 Route de Ganges, Montpellier 34059 Cedex, France.
References 1 Amadori, A., De Rossi, A., Faulkner-
Immunology Today
94
Tim Manser Dept of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
References 1 Berek, C. and Milstein, C. (1988) Immunol. Rev. 105, 5-26 2 Manser, T. (1989) J. Exp. Med. 170, 1211-1230 3 Wysocki, L.J., Gefter, M.L. and Margolies, M.N. (1990) J. Exp. Med. 172, 315-330
The review by Amadori and Chieco-Bianchi (Immunol. Today, 1990, 11,374-379) in the continuing HIV series, presented many possibilities and mechanisms of B-cell involvement in HIV infection, including the generation of antiCD4 reactivity by anti-idiotypic antibodies. The immune response to the CD4binding site of gp 120 should result in an antibody whose Fab segment has the immunological appearance of the gp120 attachment area on CD4. If this occurs, the monoclonal antibody Leu3a should detect it in an HIV-positive serum.
vol 12 No. 2 1991