Kouskoff et al.(1), in which the authors used an immunoglobulin M (IgM) nonswitchable B cell transgenic (Tg) mouse to show that the B cells could be made to react against a phage exhibiting a cross-reactive antigenic determinant of 20 amino acids in a polymeric form. This antigen was bound by the Tg antibody receptor and induced antibodies as determined in an enzymelinked immunosorbent assay (ELISA), which probably assessed low-avidity antibodies (though this was not measured or stated). The favored interpretation of Kouskoff et al. was that infectious agents can break B cell tolerance by expressing repetitive epitopes that mimic self. Surprisingly, Kouskoff et al. did not discuss earlier experiments and interpretations in which we showed that an antigen Tg mouse expressing the glycoprotein of vesicular stomatitis virus (VSV-G), and with no manipulation of the immune system, was unresponsive against VSV-G if the Tg mice were immunized with the antigen in purified form, even in complete Freund’s adjuvant (2, 3). If the same mice were exposed either to replicating VSV or formaldehyde-fixed VSV, however, a prompt, T-independent type 1 (TI-1) IgM B cell response was induced. We concluded that the Tg mice could not develop an IgM or IgG response against the Tg selfglycoprotein in an oligomeric or monomeric form, and that T help was limiting because these Tg mice were tolerant at the level of T help (4). In contrast, the polymeric form of VSV-G on the viral envelope induced B cells to produce IgM in a completely TI-1–dependent fashion in the absence of polyclonal activation (5) by cross-linking Ig receptors (6, 7). The fact that neutralization of virus requires an affinity of greater than 5 107 M 1 (8) suggests the considerable affinity of these neutralizing antibodies. This IgM response also switched to IgG because the virus particle included nuclear protein and matrix protein that in turn induced new T cell help that could be recognized in a linked fashion