In one embodiment, the invention provides methods comprising: expressing in a host cell (for e.g., a prokaryotic cell such as E. coli) a variant immunoglobulin heavy chain, said variant immunoglobulin heavy chain comprising a hinge region in which at least one, at least two, at least three, at least four (or any interger number up to all) cysteine is rendered incapable of forming a disulfide linka